Crystal structure of a hypothetical protein from Giardia lamblia. Corrigendum
The name of one of the authors in Beard et al. [(2022), Acta Cryst. F78, 59 – 65] is corrected. (Source: Acta Crystallographica Section F)
Source: Acta Crystallographica Section F - February 28, 2022 Category: Biochemistry Authors: Beard, D.K. Bristol, S. Cosby, K. Davis, A. Manning, C. Perry, L. Snapp, L. Toy, A. Wheeler, K. Young, J. Staker, B. Arakaki, T.L. Abendroth, J. Subramanian, S. Edwards, T.E. Myler, P.J. Asojo, O.A. Tags: giardiasis infectious diseases travelers' diarrhea undergraduate education and training corrigendum addenda and errata Source Type: research
Crystal structure of an inorganic pyrophosphatase from Chlamydia trachomatis D/UW-3/Cx
Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections globally and is one of the most commonly reported infections in the United States. There is a need to develop new therapeutics due to drug resistance and the failure of current treatments to clear persistent infections. Structures of potential C. trachomatis rational drug-discovery targets, including C. trachomatis inorganic pyrophosphatase (CtPPase), have been determined by the Seattle Structural Genomics Center for Infectious Disease. Inorganic pyrophosphatase hydrolyzes inorganic pyrophosphate during metabolism. Furthermore, bacte...
Source: Acta Crystallographica Section F - February 28, 2022 Category: Biochemistry Authors: Maddy, J. Staker, B.L. Subramanian, S. Abendroth, J. Edwards, T.E. Myler, P.J. Hybiske, K. Asojo, O.A. Tags: Chlamydia trachomatis inorganic pyrophosphatase infectious diseases undergraduate education and training Seattle Structural Genomics Center for Infectious Disease research communications Source Type: research
Conformational flexibility in the zinc solute-binding protein ZnuA
Zinc is an essential metal for all kingdoms of life, making its transport across the cell membrane a critical function. In bacteria, high-affinity zinc import is accomplished by ATP-binding cassette (ABC) transporters, which rely on extracellular solute-binding proteins (SBPs) of cluster A-I to acquire the metal and deliver it to the membrane permease. These systems are important for survival and virulence, making them attractive targets for the development of novel antibiotics. Citrobacter koseri is an emerging pathogen with extensive antibiotic resistance. High-affinity zinc binding to the C. koseri cluster A-I SBP ZnuA ...
Source: Acta Crystallographica Section F - February 28, 2022 Category: Biochemistry Authors: Yekwa, E.L. Serrano, F.A. Yukl, E. Tags: zinc ZnuA Citrobacter koseri solute-binding proteins ATP-binding cassette transporters research communications Source Type: research
Structural investigation of a pyrano-1,3-oxazine derivative and the phenanthridinone core moiety against BRD2 bromodomains
The BET (bromodomain and extra-terminal) family of proteins recognize the acetylated histone code on chromatin and play important roles in transcriptional co-regulation. BRD2 and BRD4, which belong to the BET family, are promising drug targets for the management of chronic diseases. The discovery of new scaffold molecules, a pyrano-1,3-oxazine derivative (NSC 328111; NS5) and phenanthridinone-based derivatives (L10 and its core moiety L10a), as inhibitors of BRD2 bromodomains BD1 and BD2, respectively, has recently been reported. The compound NS5 has a significant inhibitory effect on BRD2 in glioblastoma. Here, the crysta...
Source: Acta Crystallographica Section F - February 23, 2022 Category: Biochemistry Authors: Arole, A.H. Deshmukh, P. Sridhar, A. Padmanabhan, B. Tags: BET family bromodomain and extra-terminal family BRD2 bromodomains crystal structure pyrano-1,3-oxazine derivative phenanthridinone binding assays inhibitors research communications Source Type: research
Structural and functional analysis of the SET3 histone deacetylase complex
The SET3 complex (SET3C) is a seven-subunit histone deacetylase complex that is capable of transcriptional regulation. Methylated histone 3 marks recruit SET3C to the nucleosome, and the SET3C catalytic subunits deacetylate the histone 3 and 4 tails. There is very limited structural knowledge of the SET3C subunits, with most subunits having unknown structures or functions. Here, a catalytically active SET3 complex was endogenously purified from Saccharomyces cerevisiae and utilized for negative-stain electron microscopy (EM) to determine an apo model for the holo complex. The negative-stain EM 3D model revealed a three-lob...
Source: Acta Crystallographica Section F - February 23, 2022 Category: Biochemistry Authors: Reyes, A.A. Fishbain, S. He, Y. Tags: SET3 complex histone deacetylation electron microscopy research communications Source Type: research
6-Phosphogluconate dehydrogenase and its crystal structures
6-Phosphogluconate dehydrogenase (6PGDH; EC 1.1.1.44) catalyses the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate in the context of the oxidative part of the pentose phosphate pathway. Depending on the species, it can be a homodimer or a homotetramer. Oligomerization plays a functional role not only because the active site is at the interface between subunits but also due to the interlocking tail-modulating activity, similar to that of isocitrate dehydrogenase and malic enzyme, which catalyse a similar type of reaction. Since the pioneering crystal structure of sheep liver 6PGDH, which allowed mot...
Source: Acta Crystallographica Section F - February 23, 2022 Category: Biochemistry Authors: Hanau, S. Helliwell, J.R. Tags: 6-phosphogluconate dehydrogenase homotropic cooperativity induced fit allostery structure and function drug targets bionanotechnology topical reviews Source Type: research
Crystal structures of the ligand-binding domain of human peroxisome proliferator-activated receptor δ in complexes with phenylpropanoic acid derivatives and a pyridine carboxylic acid derivative
Peroxisome proliferator-activated receptor δ (PPAR δ ) is a member of the nuclear receptor family and regulates glucose and lipid homeostasis in a ligand-dependent manner. Numerous phenylpropanoic acid derivatives targeting three PPAR subtypes (PPAR α , PPAR γ and PPAR δ ) have been developed towards the treatment of serious diseases such as lipid-metabolism disorders. In spite of the increasing attraction of PPAR δ as a pharmaceutical target, only a limited number of protein – ligand complex structures are available. Here, four crystal structures of the ligand-binding domain of PPAR δ in complexes with phenylprop...
Source: Acta Crystallographica Section F - January 31, 2022 Category: Biochemistry Authors: Oyama, T. Takiguchi, K. Miyachi, H. Tags: nuclear receptors peroxisome proliferator-activated receptor δ PPAR ligand-binding domain research communications Source Type: research
Structural characterization of the urease accessory protein UreF from Klebsiella pneumoniae
Klebsiella pneumoniae is an opportunistic pathogen that mostly affects those with weakened immune systems. Urease is a vital enzyme that can hydrolyze urea to ammonia and carbon dioxide as a source of nitrogen for growth. Urease is also a K. pneumoniae virulence factor that enables survival of the bacterium under nutrient-limiting conditions. UreF, an important nickel-binding urease accessory protein, is involved in the insertion of Ni2+ into the active site of urease. Here, the crystal structure of UreF from K. pneumoniae (KpUreF) is reported. Functional data show that KpUreF forms a stable dimer in solution. These result...
Source: Acta Crystallographica Section F - January 31, 2022 Category: Biochemistry Authors: Liu, S. Wu, W. Zhao, Q. Liang, H. Che, S. Zhang, H. Liu, R. Zhang, Q. Bartlam, M. Tags: UreF crystal structure urease Klebsiella pneumoniae research communications Source Type: research
Crystal structure of a hypothetical protein from Giardia lamblia
This article is an educational collaboration between Hampton University and the Seattle Structural Genomics Center for Infectious Disease. (Source: Acta Crystallographica Section F)
Source: Acta Crystallographica Section F - January 28, 2022 Category: Biochemistry Authors: Beard, D.K. Bristol, S. Cosby, K. Davis, A. Manning, C. Perry, L. Snapp, L. Toy, A. Wheeler, K. Young, J. Staker, B. Arakaki, T.L. Abendroth, J. Subrahamanian, S. Edwards, T.E. Myler, P.J. Asojo, O.A. Tags: giardiasis SSGCID infectious diseases travelers' diarrhea undergraduate education and training structural genomics research communications Source Type: research
A crystal-processing machine using a deep-ultraviolet laser: application to long-wavelength native SAD experiments
While native SAD phasing is a promising method for next-generation macromolecular crystallography, it requires the collection of high-quality diffraction data using long-wavelength X-rays. The crystal itself and the noncrystalline medium around the crystal can cause background noise during long-wavelength X-ray data collection, hampering native SAD phasing. Optimizing the crystal size and shape or removing noncrystalline sample portions have thus been considered to be effective means of improving the data quality. A crystal-processing machine that uses a deep-UV laser has been developed. The machine utilizes the pulsed UV ...
Source: Acta Crystallographica Section F - January 27, 2022 Category: Biochemistry Authors: Kawano, Y. Hikita, M. Matsugaki, N. Yamamoto, M. Senda, T. Tags: X-ray crystallography deep-UV laser native SAD phasing crystal processing methods communications Source Type: research
Structural and spectroscopic characterization of CO inhibition of [NiFe]-hydrogenase from Citrobacter sp. S-77
Hydrogenases catalyze the reversible oxidation of H2. Carbon monoxide (CO) is known to be a competitive inhibitor of O2-sensitive [NiFe]-hydrogenases. Although the activities of some O2-tolerant [NiFe]-hydrogenases are unaffected by CO, the partially O2-tolerant [NiFe]-hydrogenase from Citrobacter sp. S-77 (S77-HYB) is inhibited by CO. In this work, the CO-bound state of S77-HYB was characterized by activity assays, spectroscopic techniques and X-ray crystallography. Electron paramagnetic resonance spectroscopy showed a diamagnetic Ni2+ state, and Fourier-transform infrared spectroscopy revealed the stretching vibration...
Source: Acta Crystallographica Section F - January 27, 2022 Category: Biochemistry Authors: Imanishi, T. Nishikawa, K. Taketa, M. Higuchi, K. Tai, H. Hirota, S. Hojo, H. Kawakami, T. Hataguchi, K. Matsumoto, K. Ogata, H. Higuchi, Y. Tags: [NiFe]-hydrogenases Citrobacter sp. S-77 inhibitors carbon monoxide crystal structure spectroscopy research communications Source Type: research
Crystal structure of a short-chain dehydrogenase/reductase from Burkholderia phymatum in complex with NAD
Burkholderia phymatum is an important symbiotic nitrogen-fixing betaproteobacterium. B. phymatum is beneficial, unlike other Burkholderia species, which cause disease or are potential bioagents. Structural genomics studies at the SSGCID include characterization of the structures of short-chain dehydrogenases/reductases (SDRs) from multiple Burkholderia species. The crystal structure of a short-chain dehydrogenase from B. phymatum (BpSDR) was determined in space group C2221 at a resolution of 1.80 Å . BpSDR shares less than 38% sequence identity with any known structure. The monomer is a prototypical SDR with a well co...
Source: Acta Crystallographica Section F - January 27, 2022 Category: Biochemistry Authors: Alenazi, J. Mayclin, S. Subramanian, S. Myler, P.J. Asojo, O.A. Tags: SSGCID oxidoreductases Burkholderia phymatum short-chain dehydrogenase/reductase family NAD structural genomics Seattle Structural Genomics Center for Infectious Disease research communications Source Type: research
Crystal structure of betaine aldehyde dehydrogenase from Burkholderia pseudomallei
This study reports apo and cofactor-bound crystal structures of the potential drug target betaine aldehyde dehydrogenase (BADH) from B. pseudomallei. A structural comparison identified similarities to BADH from Pseudomonas aeruginosa which is inhibited by the drug disulfiram. This preliminary analysis could facilitate drug-repurposing studies for B. pseudomallei. (Source: Acta Crystallographica Section F)
Source: Acta Crystallographica Section F - January 27, 2022 Category: Biochemistry Authors: Beard, D.K. Subramanian, S. Abendroth, J. Dranow, D.M. Edwards, T.E. Myler, P.J. Asojo, O.A. Tags: Burkholderia pseudomallei melioidosis disulfiram betaine aldehyde dehydrogenase inhibition drug repurposing research communications Source Type: research
Crystallization and low-resolution structure solution of the SALM3 – PTP σ synaptic adhesion complex
Synaptic adhesion molecules are major organizers of the neuronal network and play a crucial role in the regulation of synapse development and maintenance in the brain. Synaptic adhesion-like molecules (SALMs) and leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-PTPs) are adhesion protein families with established synaptic function. Dysfunction of several synaptic adhesion molecules has been linked to cognitive disorders such as autism spectrum disorders and schizophrenia. A recent study of the binding and complex structure of SALM3 and PTP σ using small-angle X-ray scattering revealed a 2:2 com...
Source: Acta Crystallographica Section F - December 22, 2021 Category: Biochemistry Authors: Karki, S. Kajander, T. Tags: synaptic adhesion SALM3 protein tyrosine phosphatases protein complex crystallization research communications Source Type: research
Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis
Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼ 95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-depend...
Source: Acta Crystallographica Section F - December 17, 2021 Category: Biochemistry Authors: Porter, I. Neal, T. Walker, Z. Hayes, D. Fowler, K. Billups, N. Rhoades, A. Smith, C. Smith, K. Staker, B.L. Dranow, D.M. Mayclin, S.J. Subramanian, S. Edwards, T.E. Myler, P.J. Asojo, O.A. Tags: oxidoreductases short-chain dehydrogenase/reductase family dihydrofolate reductases NADPH Brucella suis Brucella canis Seattle Structural Genomics Center for Infectious Disease SSGCID research communications Source Type: research
