cAMP signaling: a remarkably regional affair
Trends Biochem Sci. 2024 Feb 2:S0968-0004(24)00018-5. doi: 10.1016/j.tibs.2024.01.004. Online ahead of print.ABSTRACTLouis Pasteur once famously said 'in the fields of observation chance favors only the prepared mind'. Much of chance is being in the right place at the right time. This is particularly true in the crowded molecular environment of the cell where being in the right place is often more important than timing. Although Brownian motion argues that enzymes will eventually bump into substrates, this probability is greatly enhanced if both molecules reside in the same subcellular compartment. However, activation of c...
Source: Trends in Biochemical Sciences - February 3, 2024 Category: Biochemistry Authors: Andreas Bock Roshanak Irannejad John D Scott Source Type: research

Pre-twisting for improved genome modification and miRNA targeting
Trends Biochem Sci. 2024 Jan 17:S0968-0004(24)00002-1. doi: 10.1016/j.tibs.2024.01.002. Online ahead of print.ABSTRACTTwo reports by Dhuri et al. and Oyaghire et al., respectively, show that, through installing chiral centers at the backbone of the artificial nucleic acid, peptide nucleic acid (PNA), enhanced miRNA targeting and genome modification can be achieved, with important implications in fighting cancers and β-thalassemia.PMID:38238217 | DOI:10.1016/j.tibs.2024.01.002 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - January 18, 2024 Category: Biochemistry Authors: Rongguang Lu Gang Chen Source Type: research

Taking Me away: the function of phosphorylation on histone lysine demethylases
Trends Biochem Sci. 2024 Jan 16:S0968-0004(23)00299-2. doi: 10.1016/j.tibs.2023.12.004. Online ahead of print.ABSTRACTHistone lysine demethylases (KDMs) regulate eukaryotic gene transcription by catalysing the removal of methyl groups from histone proteins. These enzymes are intricately regulated by the kinase signalling system in response to internal and external stimuli. Here, we review the mechanisms by which kinase-mediated phosphorylation influence human histone KDM function. These include the changing of histone KDM subcellular localisation or chromatin binding, the altering of protein half-life, changes to histone K...
Source: Trends in Biochemical Sciences - January 17, 2024 Category: Biochemistry Authors: Nicola M Karakatsanis Joshua J Hamey Marc R Wilkins Source Type: research

Decoding anaphylatoxins: unveiling the molecular mechanisms of complement receptor activation and signaling
Trends Biochem Sci. 2024 Jan 16:S0968-0004(24)00001-X. doi: 10.1016/j.tibs.2024.01.001. Online ahead of print.ABSTRACTRecent advances in cryo-electron microscopy (Cryo-EM) have revolutionized our understanding of the complement C5a/C3a receptors that are crucial in inflammation. A recent report by Yadav et al. has elucidated the activation, ligand binding, selectivity, and signaling bias of these receptors, thereby enhancing structure-guided drug discovery. This paves the way for more effective anti-inflammatory therapies that target these receptors with unprecedented precision.PMID:38233283 | DOI:10.1016/j.tibs.2024.01.00...
Source: Trends in Biochemical Sciences - January 17, 2024 Category: Biochemistry Authors: Francisco J Fern ández M Cristina Vega Source Type: research

Interplay between the transcription preinitiation complex and the +1 nucleosome
Trends Biochem Sci. 2024 Feb;49(2):145-155. doi: 10.1016/j.tibs.2023.12.001. Epub 2024 Jan 13.ABSTRACTEukaryotic transcription starts with the assembly of a preinitiation complex (PIC) on core promoters. Flanking this region is the +1 nucleosome, the first nucleosome downstream of the core promoter. While this nucleosome is rich in epigenetic marks and plays a key role in transcription regulation, how the +1 nucleosome interacts with the transcription machinery has been a long-standing question. Here, we summarize recent structural and functional studies of the +1 nucleosome in complex with the PIC. We specifically focus o...
Source: Trends in Biochemical Sciences - January 13, 2024 Category: Biochemistry Authors: Xizi Chen Yanhui Xu Source Type: research

Advances, challenges, and opportunities in structural biology
Trends Biochem Sci. 2024 Feb;49(2):93-96. doi: 10.1016/j.tibs.2023.12.006. Epub 2024 Jan 9.NO ABSTRACTPMID:38199894 | DOI:10.1016/j.tibs.2023.12.006 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - January 10, 2024 Category: Biochemistry Authors: Basavraj Khanppnavar Rachel A North Salvador Ventura Yanhui Xu Source Type: research

Unlocking translational machinery for antitubercular drug development
Trends Biochem Sci. 2024 Jan 8:S0968-0004(23)00312-2. doi: 10.1016/j.tibs.2023.12.008. Online ahead of print.ABSTRACTTargeting translational factor proteins (TFPs) presents significant promise for the development of innovative antitubercular drugs. Previous insights from antibiotic binding mechanisms and recently solved 3D crystal structures of Mycobacterium tuberculosis (Mtb) elongation factor thermo unstable-GDP (EF-Tu-GDP), elongation factor thermo stable-EF-Tu (EF-Ts-EF-Tu), and elongation factor G-GDP (EF-G-GDP) have opened up new avenues for the design and development of potent antituberculosis (anti-TB) therapies.PM...
Source: Trends in Biochemical Sciences - January 9, 2024 Category: Biochemistry Authors: Navneet Kumar Mushtaq Ahmad Wani Chaaya Iyengar Raje Prabha Garg Source Type: research

Unlocking translational machinery for antitubercular drug development
Trends Biochem Sci. 2024 Jan 8:S0968-0004(23)00312-2. doi: 10.1016/j.tibs.2023.12.008. Online ahead of print.ABSTRACTTargeting translational factor proteins (TFPs) presents significant promise for the development of innovative antitubercular drugs. Previous insights from antibiotic binding mechanisms and recently solved 3D crystal structures of Mycobacterium tuberculosis (Mtb) elongation factor thermo unstable-GDP (EF-Tu-GDP), elongation factor thermo stable-EF-Tu (EF-Ts-EF-Tu), and elongation factor G-GDP (EF-G-GDP) have opened up new avenues for the design and development of potent antituberculosis (anti-TB) therapies.PM...
Source: Trends in Biochemical Sciences - January 9, 2024 Category: Biochemistry Authors: Navneet Kumar Mushtaq Ahmad Wani Chaaya Iyengar Raje Prabha Garg Source Type: research

The inner workings of an ancient biological clock
Trends Biochem Sci. 2024 Jan 6:S0968-0004(23)00302-X. doi: 10.1016/j.tibs.2023.12.007. Online ahead of print.ABSTRACTCircadian clocks evolved in diverse organisms as an adaptation to the daily swings in ambient light and temperature that derive from Earth's rotation. These timing systems, based on intracellular molecular oscillations, synchronize organisms' behavior and physiology with the 24-h environmental rhythm. The cyanobacterial clock serves as a special model for understanding circadian rhythms because it can be fully reconstituted in vitro. This review summarizes recent advances that leverage new biochemical, bioph...
Source: Trends in Biochemical Sciences - January 7, 2024 Category: Biochemistry Authors: Mingxu Fang Andy LiWang Susan S Golden Carrie L Partch Source Type: research

The inner workings of an ancient biological clock
Trends Biochem Sci. 2024 Jan 6:S0968-0004(23)00302-X. doi: 10.1016/j.tibs.2023.12.007. Online ahead of print.ABSTRACTCircadian clocks evolved in diverse organisms as an adaptation to the daily swings in ambient light and temperature that derive from Earth's rotation. These timing systems, based on intracellular molecular oscillations, synchronize organisms' behavior and physiology with the 24-h environmental rhythm. The cyanobacterial clock serves as a special model for understanding circadian rhythms because it can be fully reconstituted in vitro. This review summarizes recent advances that leverage new biochemical, bioph...
Source: Trends in Biochemical Sciences - January 7, 2024 Category: Biochemistry Authors: Mingxu Fang Andy LiWang Susan S Golden Carrie L Partch Source Type: research

Guidelines for organizing accessible and inclusive research retreats
Trends Biochem Sci. 2024 Jan 6:S0968-0004(23)00298-0. doi: 10.1016/j.tibs.2023.12.003. Online ahead of print.ABSTRACTResearch retreats are elements of scientific graduate training programs. Although expected to provide strong educational value, some students are reluctant to attend. Here, we identify participation barriers and provide guidelines for retreat design that minimize obstacles and establish an inclusive environment to improve attendance and enrichment for all attendees.PMID:38184399 | DOI:10.1016/j.tibs.2023.12.003 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - January 6, 2024 Category: Biochemistry Authors: Margaret J Fuller Madison R Mix Ellen Voigt Darren S Hoffmann Pamela K Geyer Source Type: research

Unlocking the biosynthesis of psychedelic-inspired indolethylamines
Trends Biochem Sci. 2023 Dec 29:S0968-0004(23)00313-4. doi: 10.1016/j.tibs.2023.12.009. Online ahead of print.ABSTRACTA recent report by Chen et al. describes the discovery of RmNMT, a highly active and promiscuous tryptamine N-methyltransferase from the cane toad, Rhinella marina. N,N-dimethyltryptamine derivatives produced by this enzyme were then evaluated for their potential to serve as next-generation treatments for mental health disorders.PMID:38160063 | DOI:10.1016/j.tibs.2023.12.009 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - December 30, 2023 Category: Biochemistry Authors: Abhishek K Sen J Andrew Jones Source Type: research

Creative approaches using proximity labeling to gain new biological insights
Trends Biochem Sci. 2023 Dec 29:S0968-0004(23)00300-6. doi: 10.1016/j.tibs.2023.12.005. Online ahead of print.ABSTRACTAt its most fundamental level, life is a collection of synchronized cellular processes driven by interactions among biomolecules. Proximity labeling has emerged as a powerful technique to capture these interactions in native settings, revealing previously unexplored elements of biology. This review highlights recent developments in proximity labeling, focusing on methods that push the fundamental technologies beyond the classic bait-prey paradigm, such as RNA-protein interactions, ligand/small-molecule-prot...
Source: Trends in Biochemical Sciences - December 30, 2023 Category: Biochemistry Authors: Ryan R Milione Bin-Bin Schell Cameron J Douglas Ciaran P Seath Source Type: research

Unlocking the biosynthesis of psychedelic-inspired indolethylamines
Trends Biochem Sci. 2023 Dec 29:S0968-0004(23)00313-4. doi: 10.1016/j.tibs.2023.12.009. Online ahead of print.ABSTRACTA recent report by Chen et al. describes the discovery of RmNMT, a highly active and promiscuous tryptamine N-methyltransferase from the cane toad, Rhinella marina. N,N-dimethyltryptamine derivatives produced by this enzyme were then evaluated for their potential to serve as next-generation treatments for mental health disorders.PMID:38160063 | DOI:10.1016/j.tibs.2023.12.009 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - December 30, 2023 Category: Biochemistry Authors: Abhishek K Sen J Andrew Jones Source Type: research

Creative approaches using proximity labeling to gain new biological insights
Trends Biochem Sci. 2023 Dec 29:S0968-0004(23)00300-6. doi: 10.1016/j.tibs.2023.12.005. Online ahead of print.ABSTRACTAt its most fundamental level, life is a collection of synchronized cellular processes driven by interactions among biomolecules. Proximity labeling has emerged as a powerful technique to capture these interactions in native settings, revealing previously unexplored elements of biology. This review highlights recent developments in proximity labeling, focusing on methods that push the fundamental technologies beyond the classic bait-prey paradigm, such as RNA-protein interactions, ligand/small-molecule-prot...
Source: Trends in Biochemical Sciences - December 30, 2023 Category: Biochemistry Authors: Ryan R Milione Bin-Bin Schell Cameron J Douglas Ciaran P Seath Source Type: research