Histone H3 N-terminal mimicry drives a novel network of methyl-effector interactions
Biochem J. 2021 May 10:BCJ20210203. doi: 10.1042/BCJ20210203. Online ahead of print.ABSTRACTThe reader ability of PHD fingers is largely limited to the recognition of the histone H3 N-terminal tail. Distinct subsets of PHDs bind either H3K4me3 (a transcriptional activator mark) or H3K4me0 (a transcriptional repressor state). Structural studies have identified common features among the different H3K4me3 effector PHDs, including 1) removal of the initiator methionine residue of H3 to prevent steric interference, 2) a groove where arginine-2 binds, and 3) an aromatic cage that engages methylated lysine-4. We hypothesize that ...
Source: The Biochemical Journal - May 10, 2021 Category: Biochemistry Authors: Jianji Chen John Horton Cari Sagum Jujun Zhou Xiaodong Cheng Mark T Bedford Source Type: research

Cancer cachexia: molecular mechanism and pharmacological management
Biochem J. 2021 May 14;478(9):1663-1688. doi: 10.1042/BCJ20201009.ABSTRACTCancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that se...
Source: The Biochemical Journal - May 10, 2021 Category: Biochemistry Authors: Yonghua Li Huan Jin Yibing Chen Ting Huang Yanjun Mi Zhengzhi Zou Source Type: research

Characterization of the Structural Determinants of the Ubiquitin-Dependent Proteasomal Degradation of Human Hepatic Tryptophan 2,3-Dioxygenase
Biochem J. 2021 May 7:BCJ20210213. doi: 10.1042/BCJ20210213. Online ahead of print.ABSTRACTHuman hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ~2.3 h, relative to an average t1/2 of ~2-3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation (UPD) pathway. Additionally, we i...
Source: The Biochemical Journal - May 7, 2021 Category: Biochemistry Authors: Yi Liu Sung Mi Kim YongQiang Wang Shay Karkashon Ariel Lewis-Ballester Syun Ru Yeh Maria Almira Correia Source Type: research

Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4
Biochem J. 2021 May 7:BCJ20210017. doi: 10.1042/BCJ20210017. Online ahead of print.ABSTRACTG:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guan...
Source: The Biochemical Journal - May 7, 2021 Category: Biochemistry Authors: Hala Ouzon-Shubeita Lillian Feigang Schmaltz Seongmin Lee Source Type: research

Characterization of the Structural Determinants of the Ubiquitin-Dependent Proteasomal Degradation of Human Hepatic Tryptophan 2,3-Dioxygenase
Biochem J. 2021 May 7:BCJ20210213. doi: 10.1042/BCJ20210213. Online ahead of print.ABSTRACTHuman hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ~2.3 h, relative to an average t1/2 of ~2-3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation (UPD) pathway. Additionally, we i...
Source: The Biochemical Journal - May 7, 2021 Category: Biochemistry Authors: Yi Liu Sung Mi Kim YongQiang Wang Shay Karkashon Ariel Lewis-Ballester Syun Ru Yeh Maria Almira Correia Source Type: research

Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4
Biochem J. 2021 May 7:BCJ20210017. doi: 10.1042/BCJ20210017. Online ahead of print.ABSTRACTG:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guan...
Source: The Biochemical Journal - May 7, 2021 Category: Biochemistry Authors: Hala Ouzon-Shubeita Lillian Feigang Schmaltz Seongmin Lee Source Type: research

Characterization of the Structural Determinants of the Ubiquitin-Dependent Proteasomal Degradation of Human Hepatic Tryptophan 2,3-Dioxygenase
Biochem J. 2021 May 7:BCJ20210213. doi: 10.1042/BCJ20210213. Online ahead of print.ABSTRACTHuman hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ~2.3 h, relative to an average t1/2 of ~2-3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation (UPD) pathway. Additionally, we i...
Source: The Biochemical Journal - May 7, 2021 Category: Biochemistry Authors: Yi Liu Sung Mi Kim YongQiang Wang Shay Karkashon Ariel Lewis-Ballester Syun Ru Yeh Maria Almira Correia Source Type: research

Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4
Biochem J. 2021 May 7:BCJ20210017. doi: 10.1042/BCJ20210017. Online ahead of print.ABSTRACTG:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guan...
Source: The Biochemical Journal - May 7, 2021 Category: Biochemistry Authors: Hala Ouzon-Shubeita Lillian Feigang Schmaltz Seongmin Lee Source Type: research

Internalization and membrane activity of the antimicrobial peptide CGA-N12
Biochem J. 2021 May 6:BCJ20201006. doi: 10.1042/BCJ20201006. Online ahead of print.ABSTRACTAntimicrobial peptides (AMPs) are conventional antibiotic alternatives due to their broad-spectrum antimicrobial activities and special mechanisms of action against pathogens. The antifungal peptide CGA-N12 was originally derived from human chromogranin A (CGA) and consists of the 65th to 76th amino acids of the CGA N-terminal region. In the present study, we found that CGA-N12 had fungicidal activity and exhibited time-dependent inhibition activity against Candida tropicalis. CGA-N12 entered the cells to exert its antagonist activit...
Source: The Biochemical Journal - May 6, 2021 Category: Biochemistry Authors: Ruifang Li Mengke Tao Shang Li Xueqin Wang Yanhui Yang Lianfeng Mo Kaidi Zhang Ao Wei Liang Huang Source Type: research

Unique C-terminal extension and interactome of Mycobacterium tuberculosis GlmU impacts its in vivo function and the survival of the pathogen
Biochem J. 2021 May 6:BCJ20210170. doi: 10.1042/BCJ20210170. Online ahead of print.ABSTRACTN-acetyl glucosamine-1-phosphate uridyltransferase (GlmU) is a bifunctional enzyme involved in the biosynthesis of Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a critical precursor for the synthesis of peptidoglycan and other cell wall components. The absence of a homolog in eukaryotes makes GlmU an attractive target for therapeutic intervention. Mycobacterium tuberculosis GlmU (GlmUMt) has features, such as a C-terminal extension, that are not present in GlmU orthologs from other bacteria. Here, we set out to ...
Source: The Biochemical Journal - May 6, 2021 Category: Biochemistry Authors: Meetu Kumar Agarwal Vijay Kumar Soni Suresh Kumar Biplab Singha Vinay Kumar Nandicoori Source Type: research

Internalization and membrane activity of the antimicrobial peptide CGA-N12
Biochem J. 2021 May 6:BCJ20201006. doi: 10.1042/BCJ20201006. Online ahead of print.ABSTRACTAntimicrobial peptides (AMPs) are conventional antibiotic alternatives due to their broad-spectrum antimicrobial activities and special mechanisms of action against pathogens. The antifungal peptide CGA-N12 was originally derived from human chromogranin A (CGA) and consists of the 65th to 76th amino acids of the CGA N-terminal region. In the present study, we found that CGA-N12 had fungicidal activity and exhibited time-dependent inhibition activity against Candida tropicalis. CGA-N12 entered the cells to exert its antagonist activit...
Source: The Biochemical Journal - May 6, 2021 Category: Biochemistry Authors: Ruifang Li Mengke Tao Shang Li Xueqin Wang Yanhui Yang Lianfeng Mo Kaidi Zhang Ao Wei Liang Huang Source Type: research

Unique C-terminal extension and interactome of Mycobacterium tuberculosis GlmU impacts its in vivo function and the survival of the pathogen
Biochem J. 2021 May 6:BCJ20210170. doi: 10.1042/BCJ20210170. Online ahead of print.ABSTRACTN-acetyl glucosamine-1-phosphate uridyltransferase (GlmU) is a bifunctional enzyme involved in the biosynthesis of Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a critical precursor for the synthesis of peptidoglycan and other cell wall components. The absence of a homolog in eukaryotes makes GlmU an attractive target for therapeutic intervention. Mycobacterium tuberculosis GlmU (GlmUMt) has features, such as a C-terminal extension, that are not present in GlmU orthologs from other bacteria. Here, we set out to ...
Source: The Biochemical Journal - May 6, 2021 Category: Biochemistry Authors: Meetu Kumar Agarwal Vijay Kumar Soni Suresh Kumar Biplab Singha Vinay Kumar Nandicoori Source Type: research

The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice
Biochem J. 2021 May 4:BCJ20210212. doi: 10.1042/BCJ20210212. Online ahead of print.ABSTRACTSaliva, while often taken for granted, is indispensable for oral health and overall well-being, as inferred from the significant impairments suffered by patients with salivary gland dysfunction. Here, we show that treatment with several structurally-distinct PAN-PDE4 inhibitors, but not a PDE3 inhibitor, induces saliva secretion in mice, indicating it is a class-effect of PDE4 inhibitors. In anesthetized mice, while neuronal regulations are suppressed, PDE4 inhibition potentiates a β-adrenoceptor-induced salivation, that is abla...
Source: The Biochemical Journal - May 4, 2021 Category: Biochemistry Authors: Abigail Boyd Ileana V Aragon Lina Abou Saleh Dylan Southers Wito Richter Source Type: research

The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice
Biochem J. 2021 May 4:BCJ20210212. doi: 10.1042/BCJ20210212. Online ahead of print.ABSTRACTSaliva, while often taken for granted, is indispensable for oral health and overall well-being, as inferred from the significant impairments suffered by patients with salivary gland dysfunction. Here, we show that treatment with several structurally-distinct PAN-PDE4 inhibitors, but not a PDE3 inhibitor, induces saliva secretion in mice, indicating it is a class-effect of PDE4 inhibitors. In anesthetized mice, while neuronal regulations are suppressed, PDE4 inhibition potentiates a β-adrenoceptor-induced salivation, that is abla...
Source: The Biochemical Journal - May 4, 2021 Category: Biochemistry Authors: Abigail Boyd Ileana V Aragon Lina Abou Saleh Dylan Southers Wito Richter Source Type: research

Kinase-anchoring proteins in ciliary signal transduction
This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.PMID:33909027 | DOI:10.1042/BCJ20200869 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: Janani Gopalan Linda Wordeman John D Scott Source Type: research

Classification, structural biology, and applications of mucin domain-targeting proteases
Biochem J. 2021 Apr 30;478(8):1585-1603. doi: 10.1042/BCJ20200607.ABSTRACTEpithelial surfaces throughout the body are coated by mucins, a class of proteins carrying domains characterized by a high density of O-glycosylated serine and threonine residues. The resulting mucosal layers form crucial host-microbe interfaces that prevent the translocation of microbes while also selecting for distinct bacteria via the presented glycan repertoire. The intricate interplay between mucus production and breakdown thus determines the composition of the microbiota maintained within these mucosal environments, which can have a large influ...
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: D Judy Shon Angel Kuo Michael J Ferracane Stacy A Malaker Source Type: research

Kinase-anchoring proteins in ciliary signal transduction
This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.PMID:33909027 | DOI:10.1042/BCJ20200869 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: Janani Gopalan Linda Wordeman John D Scott Source Type: research

Classification, structural biology, and applications of mucin domain-targeting proteases
Biochem J. 2021 Apr 30;478(8):1585-1603. doi: 10.1042/BCJ20200607.ABSTRACTEpithelial surfaces throughout the body are coated by mucins, a class of proteins carrying domains characterized by a high density of O-glycosylated serine and threonine residues. The resulting mucosal layers form crucial host-microbe interfaces that prevent the translocation of microbes while also selecting for distinct bacteria via the presented glycan repertoire. The intricate interplay between mucus production and breakdown thus determines the composition of the microbiota maintained within these mucosal environments, which can have a large influ...
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: D Judy Shon Angel Kuo Michael J Ferracane Stacy A Malaker Source Type: research

Kinase-anchoring proteins in ciliary signal transduction
This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.PMID:33909027 | DOI:10.1042/BCJ20200869 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: Janani Gopalan Linda Wordeman John D Scott Source Type: research

Classification, structural biology, and applications of mucin domain-targeting proteases
Biochem J. 2021 Apr 30;478(8):1585-1603. doi: 10.1042/BCJ20200607.ABSTRACTEpithelial surfaces throughout the body are coated by mucins, a class of proteins carrying domains characterized by a high density of O-glycosylated serine and threonine residues. The resulting mucosal layers form crucial host-microbe interfaces that prevent the translocation of microbes while also selecting for distinct bacteria via the presented glycan repertoire. The intricate interplay between mucus production and breakdown thus determines the composition of the microbiota maintained within these mucosal environments, which can have a large influ...
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: D Judy Shon Angel Kuo Michael J Ferracane Stacy A Malaker Source Type: research

Kinase-anchoring proteins in ciliary signal transduction
This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.PMID:33909027 | DOI:10.1042/BCJ20200869 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: Janani Gopalan Linda Wordeman John D Scott Source Type: research

Classification, structural biology, and applications of mucin domain-targeting proteases
Biochem J. 2021 Apr 30;478(8):1585-1603. doi: 10.1042/BCJ20200607.ABSTRACTEpithelial surfaces throughout the body are coated by mucins, a class of proteins carrying domains characterized by a high density of O-glycosylated serine and threonine residues. The resulting mucosal layers form crucial host-microbe interfaces that prevent the translocation of microbes while also selecting for distinct bacteria via the presented glycan repertoire. The intricate interplay between mucus production and breakdown thus determines the composition of the microbiota maintained within these mucosal environments, which can have a large influ...
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: D Judy Shon Angel Kuo Michael J Ferracane Stacy A Malaker Source Type: research

Kinase-anchoring proteins in ciliary signal transduction
This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.PMID:33909027 | DOI:10.1042/BCJ20200869 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: Janani Gopalan Linda Wordeman John D Scott Source Type: research

Classification, structural biology, and applications of mucin domain-targeting proteases
Biochem J. 2021 Apr 30;478(8):1585-1603. doi: 10.1042/BCJ20200607.ABSTRACTEpithelial surfaces throughout the body are coated by mucins, a class of proteins carrying domains characterized by a high density of O-glycosylated serine and threonine residues. The resulting mucosal layers form crucial host-microbe interfaces that prevent the translocation of microbes while also selecting for distinct bacteria via the presented glycan repertoire. The intricate interplay between mucus production and breakdown thus determines the composition of the microbiota maintained within these mucosal environments, which can have a large influ...
Source: The Biochemical Journal - April 28, 2021 Category: Biochemistry Authors: D Judy Shon Angel Kuo Michael J Ferracane Stacy A Malaker Source Type: research

FATP4 inactivation in cultured macrophages attenuates M1- and ER stress-induced cytokine release via a metabolic shift towards triacylglycerides
Biochem J. 2021 Apr 26:BCJ20210155. doi: 10.1042/BCJ20210155. Online ahead of print.ABSTRACTFatty acid transport protein 4 (FATP4) belongs to a family of acyl-CoA synthetases which activate long-chain fatty acids into acyl-CoAs subsequently used in specific metabolic pathways. Patients with FATP4 mutations and Fatp4-null mice show thick desquamating skin and other complications, however, FATP4 role on macrophage functions has not been studied. We here determined whether the levels of macrophage glycerophospholipids, sphingolipids including ceramides, triacylglycerides, and cytokine release could be altered by FATP4 inactiv...
Source: The Biochemical Journal - April 26, 2021 Category: Biochemistry Authors: Yuling Zhang Ning Wu Hongying Gan-Schreier Feng Xu Sabine Tuma-Kellner Simone Staffer Jessica Seessle Uta Merle Walee Chamulitrat Source Type: research

Enhanced Plant-microbe Remediation of PCBs in Soil using Enzyme Modification Technique Combined with Molecular Docking and Molecular Dynamics
Biochem J. 2021 Apr 26:BCJ20210104. doi: 10.1042/BCJ20210104. Online ahead of print.ABSTRACTThe study on the enhanced mechanisms of the enzymes involved in plant absorption, plant degradation, and microbial mineralization in the remediation of soils contaminated with polychlorinated biphenyls (PCBs) is of great significance for the application of plant-microbe combined remediation technique in PCB-contaminated soils. The present study first used a combination of molecular docking and molecular dynamics methods to calculate the effects of the plant absorption enzyme, plant degradation enzyme, and microbial mineralization en...
Source: The Biochemical Journal - April 26, 2021 Category: Biochemistry Authors: Minghao Li Wei He Yu Li Source Type: research

FATP4 inactivation in cultured macrophages attenuates M1- and ER stress-induced cytokine release via a metabolic shift towards triacylglycerides
Biochem J. 2021 Apr 26:BCJ20210155. doi: 10.1042/BCJ20210155. Online ahead of print.ABSTRACTFatty acid transport protein 4 (FATP4) belongs to a family of acyl-CoA synthetases which activate long-chain fatty acids into acyl-CoAs subsequently used in specific metabolic pathways. Patients with FATP4 mutations and Fatp4-null mice show thick desquamating skin and other complications, however, FATP4 role on macrophage functions has not been studied. We here determined whether the levels of macrophage glycerophospholipids, sphingolipids including ceramides, triacylglycerides, and cytokine release could be altered by FATP4 inactiv...
Source: The Biochemical Journal - April 26, 2021 Category: Biochemistry Authors: Yuling Zhang Ning Wu Hongying Gan-Schreier Feng Xu Sabine Tuma-Kellner Simone Staffer Jessica Seessle Uta Merle Walee Chamulitrat Source Type: research

Enhanced Plant-microbe Remediation of PCBs in Soil using Enzyme Modification Technique Combined with Molecular Docking and Molecular Dynamics
Biochem J. 2021 Apr 26:BCJ20210104. doi: 10.1042/BCJ20210104. Online ahead of print.ABSTRACTThe study on the enhanced mechanisms of the enzymes involved in plant absorption, plant degradation, and microbial mineralization in the remediation of soils contaminated with polychlorinated biphenyls (PCBs) is of great significance for the application of plant-microbe combined remediation technique in PCB-contaminated soils. The present study first used a combination of molecular docking and molecular dynamics methods to calculate the effects of the plant absorption enzyme, plant degradation enzyme, and microbial mineralization en...
Source: The Biochemical Journal - April 26, 2021 Category: Biochemistry Authors: Minghao Li Wei He Yu Li Source Type: research

Protecting P-type plasma membrane H+-ATPases from ROS
Biochem J. 2021 Apr 30;478(8):1511-1513. doi: 10.1042/BCJ20210109.ABSTRACTP-type ATPase are ubiquitous transport proteins across all kingdoms of life. These proteins share a common mechanism involving phosphorylation of an invariant aspartate to facilitate movement of substrates from protons to phospholipids across cellular membranes. In this issue of the Biochemical Journal, Welle et al. identify a conserved cysteine near the functionally critical aspartate of P-type plasma membrane H+-ATPases that protects the protein from reactive oxygen species.PMID:33881485 | DOI:10.1042/BCJ20210109 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Sarah C Stainbrook Joseph M Jez Source Type: research

Pyrophosphate as an alternative energy currency in plants
Biochem J. 2021 Apr 30;478(8):1515-1524. doi: 10.1042/BCJ20200940.ABSTRACTIn the conditions of [Mg2+] elevation that occur, in particular, under low oxygen stress and are the consequence of the decrease in [ATP] and increase in [ADP] and [AMP], pyrophosphate (PPi) can function as an alternative energy currency in plant cells. In addition to its production by various metabolic pathways, PPi can be synthesized in the combined reactions of pyruvate, phosphate dikinase (PPDK) and pyruvate kinase (PK) by so-called PK/PPDK substrate cycle, and in the reverse reaction of membrane-bound H+-pyrophosphatase, which uses the energy of...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Abir U Igamberdiev Leszek A Kleczkowski Source Type: research

Anti-glycan antibodies: roles in human disease
Biochem J. 2021 Apr 30;478(8):1485-1509. doi: 10.1042/BCJ20200610.ABSTRACTCarbohydrate-binding antibodies play diverse and critical roles in human health. Endogenous carbohydrate-binding antibodies that recognize bacterial, fungal, and other microbial carbohydrates prevent systemic infections and help maintain microbiome homeostasis. Anti-glycan antibodies can have both beneficial and detrimental effects. For example, alloantibodies to ABO blood group carbohydrates can help reduce the spread of some infectious diseases, but they also impose limitations for blood transfusions. Antibodies that recognize self-glycans can cont...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: J Sebastian Temme Dorothy L Butler Jeffrey C Gildersleeve Source Type: research

Insights into the mismatch discrimination mechanism of Y-family DNA polymerase Dpo4
Biochem J. 2021 Apr 21:BCJ20210162. doi: 10.1042/BCJ20210162. Online ahead of print.ABSTRACTNucleobases within DNA are attacked by reactive oxygen species to produce 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major oxidative lesions. The high mutagenicity of oxoG is attributed to the lesion's ability to adopt syn-oxoG:anti-dA with Watson-Crick-like geometry. Recent studies have revealed that Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) inserts nucleotide opposite oxoA in an error-prone manner and accommodates syn-oxoA:anti-dGTP with Watson-Crick-like geometry, highlighting a promutagenic ...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Hunmin Jung Seongmin Lee Source Type: research

Protecting P-type plasma membrane H+-ATPases from ROS
Biochem J. 2021 Apr 30;478(8):1511-1513. doi: 10.1042/BCJ20210109.ABSTRACTP-type ATPase are ubiquitous transport proteins across all kingdoms of life. These proteins share a common mechanism involving phosphorylation of an invariant aspartate to facilitate movement of substrates from protons to phospholipids across cellular membranes. In this issue of the Biochemical Journal, Welle et al. identify a conserved cysteine near the functionally critical aspartate of P-type plasma membrane H+-ATPases that protects the protein from reactive oxygen species.PMID:33881485 | DOI:10.1042/BCJ20210109 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Sarah C Stainbrook Joseph M Jez Source Type: research

Pyrophosphate as an alternative energy currency in plants
Biochem J. 2021 Apr 30;478(8):1515-1524. doi: 10.1042/BCJ20200940.ABSTRACTIn the conditions of [Mg2+] elevation that occur, in particular, under low oxygen stress and are the consequence of the decrease in [ATP] and increase in [ADP] and [AMP], pyrophosphate (PPi) can function as an alternative energy currency in plant cells. In addition to its production by various metabolic pathways, PPi can be synthesized in the combined reactions of pyruvate, phosphate dikinase (PPDK) and pyruvate kinase (PK) by so-called PK/PPDK substrate cycle, and in the reverse reaction of membrane-bound H+-pyrophosphatase, which uses the energy of...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Abir U Igamberdiev Leszek A Kleczkowski Source Type: research

Anti-glycan antibodies: roles in human disease
Biochem J. 2021 Apr 30;478(8):1485-1509. doi: 10.1042/BCJ20200610.ABSTRACTCarbohydrate-binding antibodies play diverse and critical roles in human health. Endogenous carbohydrate-binding antibodies that recognize bacterial, fungal, and other microbial carbohydrates prevent systemic infections and help maintain microbiome homeostasis. Anti-glycan antibodies can have both beneficial and detrimental effects. For example, alloantibodies to ABO blood group carbohydrates can help reduce the spread of some infectious diseases, but they also impose limitations for blood transfusions. Antibodies that recognize self-glycans can cont...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: J Sebastian Temme Dorothy L Butler Jeffrey C Gildersleeve Source Type: research

Insights into the mismatch discrimination mechanism of Y-family DNA polymerase Dpo4
Biochem J. 2021 Apr 21:BCJ20210162. doi: 10.1042/BCJ20210162. Online ahead of print.ABSTRACTNucleobases within DNA are attacked by reactive oxygen species to produce 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major oxidative lesions. The high mutagenicity of oxoG is attributed to the lesion's ability to adopt syn-oxoG:anti-dA with Watson-Crick-like geometry. Recent studies have revealed that Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) inserts nucleotide opposite oxoA in an error-prone manner and accommodates syn-oxoA:anti-dGTP with Watson-Crick-like geometry, highlighting a promutagenic ...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Hunmin Jung Seongmin Lee Source Type: research

Protecting P-type plasma membrane H+-ATPases from ROS
Biochem J. 2021 Apr 30;478(8):1511-1513. doi: 10.1042/BCJ20210109.ABSTRACTP-type ATPase are ubiquitous transport proteins across all kingdoms of life. These proteins share a common mechanism involving phosphorylation of an invariant aspartate to facilitate movement of substrates from protons to phospholipids across cellular membranes. In this issue of the Biochemical Journal, Welle et al. identify a conserved cysteine near the functionally critical aspartate of P-type plasma membrane H+-ATPases that protects the protein from reactive oxygen species.PMID:33881485 | DOI:10.1042/BCJ20210109 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Sarah C Stainbrook Joseph M Jez Source Type: research

Pyrophosphate as an alternative energy currency in plants
Biochem J. 2021 Apr 30;478(8):1515-1524. doi: 10.1042/BCJ20200940.ABSTRACTIn the conditions of [Mg2+] elevation that occur, in particular, under low oxygen stress and are the consequence of the decrease in [ATP] and increase in [ADP] and [AMP], pyrophosphate (PPi) can function as an alternative energy currency in plant cells. In addition to its production by various metabolic pathways, PPi can be synthesized in the combined reactions of pyruvate, phosphate dikinase (PPDK) and pyruvate kinase (PK) by so-called PK/PPDK substrate cycle, and in the reverse reaction of membrane-bound H+-pyrophosphatase, which uses the energy of...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Abir U Igamberdiev Leszek A Kleczkowski Source Type: research

Anti-glycan antibodies: roles in human disease
Biochem J. 2021 Apr 30;478(8):1485-1509. doi: 10.1042/BCJ20200610.ABSTRACTCarbohydrate-binding antibodies play diverse and critical roles in human health. Endogenous carbohydrate-binding antibodies that recognize bacterial, fungal, and other microbial carbohydrates prevent systemic infections and help maintain microbiome homeostasis. Anti-glycan antibodies can have both beneficial and detrimental effects. For example, alloantibodies to ABO blood group carbohydrates can help reduce the spread of some infectious diseases, but they also impose limitations for blood transfusions. Antibodies that recognize self-glycans can cont...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: J Sebastian Temme Dorothy L Butler Jeffrey C Gildersleeve Source Type: research

Insights into the mismatch discrimination mechanism of Y-family DNA polymerase Dpo4
Biochem J. 2021 Apr 21:BCJ20210162. doi: 10.1042/BCJ20210162. Online ahead of print.ABSTRACTNucleobases within DNA are attacked by reactive oxygen species to produce 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major oxidative lesions. The high mutagenicity of oxoG is attributed to the lesion's ability to adopt syn-oxoG:anti-dA with Watson-Crick-like geometry. Recent studies have revealed that Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) inserts nucleotide opposite oxoA in an error-prone manner and accommodates syn-oxoA:anti-dGTP with Watson-Crick-like geometry, highlighting a promutagenic ...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Hunmin Jung Seongmin Lee Source Type: research

Protecting P-type plasma membrane H+-ATPases from ROS
Biochem J. 2021 Apr 30;478(8):1511-1513. doi: 10.1042/BCJ20210109.ABSTRACTP-type ATPase are ubiquitous transport proteins across all kingdoms of life. These proteins share a common mechanism involving phosphorylation of an invariant aspartate to facilitate movement of substrates from protons to phospholipids across cellular membranes. In this issue of the Biochemical Journal, Welle et al. identify a conserved cysteine near the functionally critical aspartate of P-type plasma membrane H+-ATPases that protects the protein from reactive oxygen species.PMID:33881485 | DOI:10.1042/BCJ20210109 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Sarah C Stainbrook Joseph M Jez Source Type: research

Pyrophosphate as an alternative energy currency in plants
Biochem J. 2021 Apr 30;478(8):1515-1524. doi: 10.1042/BCJ20200940.ABSTRACTIn the conditions of [Mg2+] elevation that occur, in particular, under low oxygen stress and are the consequence of the decrease in [ATP] and increase in [ADP] and [AMP], pyrophosphate (PPi) can function as an alternative energy currency in plant cells. In addition to its production by various metabolic pathways, PPi can be synthesized in the combined reactions of pyruvate, phosphate dikinase (PPDK) and pyruvate kinase (PK) by so-called PK/PPDK substrate cycle, and in the reverse reaction of membrane-bound H+-pyrophosphatase, which uses the energy of...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Abir U Igamberdiev Leszek A Kleczkowski Source Type: research

Anti-glycan antibodies: roles in human disease
Biochem J. 2021 Apr 30;478(8):1485-1509. doi: 10.1042/BCJ20200610.ABSTRACTCarbohydrate-binding antibodies play diverse and critical roles in human health. Endogenous carbohydrate-binding antibodies that recognize bacterial, fungal, and other microbial carbohydrates prevent systemic infections and help maintain microbiome homeostasis. Anti-glycan antibodies can have both beneficial and detrimental effects. For example, alloantibodies to ABO blood group carbohydrates can help reduce the spread of some infectious diseases, but they also impose limitations for blood transfusions. Antibodies that recognize self-glycans can cont...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: J Sebastian Temme Dorothy L Butler Jeffrey C Gildersleeve Source Type: research

Insights into the mismatch discrimination mechanism of Y-family DNA polymerase Dpo4
Biochem J. 2021 Apr 21:BCJ20210162. doi: 10.1042/BCJ20210162. Online ahead of print.ABSTRACTNucleobases within DNA are attacked by reactive oxygen species to produce 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major oxidative lesions. The high mutagenicity of oxoG is attributed to the lesion's ability to adopt syn-oxoG:anti-dA with Watson-Crick-like geometry. Recent studies have revealed that Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) inserts nucleotide opposite oxoA in an error-prone manner and accommodates syn-oxoA:anti-dGTP with Watson-Crick-like geometry, highlighting a promutagenic ...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Hunmin Jung Seongmin Lee Source Type: research

Protecting P-type plasma membrane H+-ATPases from ROS
Biochem J. 2021 Apr 30;478(8):1511-1513. doi: 10.1042/BCJ20210109.ABSTRACTP-type ATPase are ubiquitous transport proteins across all kingdoms of life. These proteins share a common mechanism involving phosphorylation of an invariant aspartate to facilitate movement of substrates from protons to phospholipids across cellular membranes. In this issue of the Biochemical Journal, Welle et al. identify a conserved cysteine near the functionally critical aspartate of P-type plasma membrane H+-ATPases that protects the protein from reactive oxygen species.PMID:33881485 | DOI:10.1042/BCJ20210109 (Source: The Biochemical Journal)
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Sarah C Stainbrook Joseph M Jez Source Type: research

Pyrophosphate as an alternative energy currency in plants
Biochem J. 2021 Apr 30;478(8):1515-1524. doi: 10.1042/BCJ20200940.ABSTRACTIn the conditions of [Mg2+] elevation that occur, in particular, under low oxygen stress and are the consequence of the decrease in [ATP] and increase in [ADP] and [AMP], pyrophosphate (PPi) can function as an alternative energy currency in plant cells. In addition to its production by various metabolic pathways, PPi can be synthesized in the combined reactions of pyruvate, phosphate dikinase (PPDK) and pyruvate kinase (PK) by so-called PK/PPDK substrate cycle, and in the reverse reaction of membrane-bound H+-pyrophosphatase, which uses the energy of...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Abir U Igamberdiev Leszek A Kleczkowski Source Type: research

Anti-glycan antibodies: roles in human disease
Biochem J. 2021 Apr 30;478(8):1485-1509. doi: 10.1042/BCJ20200610.ABSTRACTCarbohydrate-binding antibodies play diverse and critical roles in human health. Endogenous carbohydrate-binding antibodies that recognize bacterial, fungal, and other microbial carbohydrates prevent systemic infections and help maintain microbiome homeostasis. Anti-glycan antibodies can have both beneficial and detrimental effects. For example, alloantibodies to ABO blood group carbohydrates can help reduce the spread of some infectious diseases, but they also impose limitations for blood transfusions. Antibodies that recognize self-glycans can cont...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: J Sebastian Temme Dorothy L Butler Jeffrey C Gildersleeve Source Type: research

Insights into the mismatch discrimination mechanism of Y-family DNA polymerase Dpo4
Biochem J. 2021 Apr 21:BCJ20210162. doi: 10.1042/BCJ20210162. Online ahead of print.ABSTRACTNucleobases within DNA are attacked by reactive oxygen species to produce 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major oxidative lesions. The high mutagenicity of oxoG is attributed to the lesion's ability to adopt syn-oxoG:anti-dA with Watson-Crick-like geometry. Recent studies have revealed that Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) inserts nucleotide opposite oxoA in an error-prone manner and accommodates syn-oxoA:anti-dGTP with Watson-Crick-like geometry, highlighting a promutagenic ...
Source: The Biochemical Journal - April 21, 2021 Category: Biochemistry Authors: Hunmin Jung Seongmin Lee Source Type: research

Characterization of tolloid-mediated cleavage of the GDF8 procomplex
Biochem J. 2021 Apr 20:BCJ20210054. doi: 10.1042/BCJ20210054. Online ahead of print.ABSTRACTGrowth differentiation factor 8 (GDF8), a.k.a. myostatin, is a member of the larger TGFβ superfamily of signaling ligands. GDF8 has been well characterized as a negative regulator of muscle mass. After synthesis, GDF8 is held latent by a noncovalent complex between the N-terminal prodomain and the signaling ligand. Activation of latent GDF8 requires proteolytic cleavage of the prodomain at residue D99 by a member of the tolloid family of metalloproteases. While tolloid proteases cleave multiple substrates, they lack a conserved...
Source: The Biochemical Journal - April 20, 2021 Category: Biochemistry Authors: Jason C McCoy Erich J Goebel Thomas B Thompson Source Type: research

Integrin αVβ1 Regulates Procollagen I Production through a Non-canonical Transforming Growth Factor β Signaling Pathway in Human Hepatic Stellate Cells
Biochem J. 2021 Apr 20:BCJ20200749. doi: 10.1042/BCJ20200749. Online ahead of print.ABSTRACTHepatic stellate cells (HSCs) are thought to play key roles in the development of liver fibrosis. Extensive evidence has established the concept that αV integrins are involved in the activation of latent transforming growth factor β (TGF-β), a master regulator of the fibrotic signaling cascade. Based on mRNA and protein expression profiling data, we found that αVβ1 integrin is the most abundant member of the αV integrin family in either quiescent or TGF-β1-activated primary human HSCs. Unexpecte...
Source: The Biochemical Journal - April 20, 2021 Category: Biochemistry Authors: Zuoning Han Yanling Ma Gary Cao Zhengping Ma Ruihua Chen Mary Ellen Cvijic Dong Cheng Source Type: research