Article
Biochemistry & Molecular Biology
Suwon Kim, Seri Jo, Mi-Sun Kim, Dong Hae Shin
Summary: The enzyme BpHldC from Burkholderia pseudomallei is a promising target for anti-melioidosis therapy, with the compound ChemBridge 7929959 showing the most effective inhibitory activity. This compound, with a terminal benzyl group, demonstrated medium affinity due to its binding to the substrate pocket. Moreover, ChemBridge compounds have the potential to be developed as potent anti-melioidosis agents with a novel inhibitory concept.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Suwon Kim, Seri Jo, Mi-Sun Kim, Heejin Kam, Dong Hae Shin
Summary: This study demonstrates the inhibitory activity of flavonoids against an essential enzyme in the biosynthesis pathway of B. pseudomallei, suggesting EGCG and myricetin as potential templates for antibiotic development against melioidosis.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Dao Feng Xiang, James B. Thoden, Manas K. Ghosh, Hazel M. Holden, Frank M. Raushel
Summary: Campylobacter jejuni, a common cause of food poisoning, has different serotypes with distinct sugar sequences and modifications in its capsular polysaccharide. This study reports the characterization and structure of an enzyme involved in the synthesis of the capsular polysaccharide in C. jejuni 81-176.
Article
Biochemistry & Molecular Biology
Konstantin Potapov, Roman A. Novikov, Pavel N. Solyev, Sergey N. Kochetkov, Alexander A. Makarov, Vladimir A. Mitkevich
Summary: The article highlights the important role of heptose phosphates in immune system activation and the significance of obtaining a substantial amount of heptose phosphates for biological studies through optimizing synthetic methods. By developing a new synthesis approach, efficiency has been improved and the number of steps reduced, potentially offering practical value for further biological screening.
Article
Biochemistry & Molecular Biology
Jamison P. Huddleston, Thomas K. Anderson, Nicholas M. Girardi, James B. Thoden, Zane Taylor, Hazel M. Holden, Frank M. Raushel
Summary: Campylobacter jejuni is coated with a capsular polysaccharide (CPS) on its exterior cell surface, whose monosaccharide components' identity and sequences are strain-dependent. Proteins such as Cj1430 play crucial roles in catalyzing important reactions for bacterial survival.
Article
Chemistry, Organic
Shuai Meng, Ishani Lakshika Hettiarachchi, Bishwa Raj Bhetuwal, Prakash Thapa, Jianglong Zhu
Summary: This method enables the stereoselective synthesis of D-glycero- and L-glycero-beta-D-mannoheptosides, and has been utilized in the total synthesis of a tetrasaccharide repeat unit of Bacillus thermoaerophilus surface-layer glycoprotein.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alexander S. Riegert, Tamari Narindoshvili, Nicole E. Platzer, Frank M. Raushel
Summary: Campylobacter jejuni is a pathogenic bacterium found in the intestines of chickens and other farm animals. The infection caused by this bacterium can result in campylobacteriosis, which leads to symptoms such as nausea, diarrhea, fever, cramps, and even death. Recent research has focused on the enzymes involved in the synthesis of a phosphorylated glucuronamide intermediate in C. jejuni, and the final modifying enzyme Cj1435 has been characterized.
Article
Immunology
Sue-Fen Chiu, Kai-Wen Teng, Po-Chuan Wang, Hsin-Yu Chung, Chun-Jen Wang, Hui-Chun Cheng, Mou-Chieh Kao
Summary: The HP0860 gene in Helicobacter pylori plays a crucial role in bacterial pathogenesis and virulence, with its knockout mutant showing reduced toxicity and infectivity. These findings provide insights into potential therapeutic strategies for combating H. pylori infection.
Article
Biochemistry & Molecular Biology
Vijayakumar Rajendran, Karthe Ponnuraj
Summary: Helicobacter pylori is a bacteria that causes peptic ulcer and gastric cancer. The study focused on the development of new drugs against the pathogen using molecular modeling and virtual screening. A potential compound with higher affinity than the substrate was identified and further molecular dynamics simulations were conducted.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Alexander S. Shashkov, Nikolay P. Arbatsky, Sof'ya N. Senchenkova, Andrei Perepelov, Alexander O. Chizhov, Andrei S. Dmitrenok, Mikhail M. Shneider, Yuriy A. Knirel
Summary: This study reports the identification of a new isomer in the capsular polysaccharide of Acinetobacter baumannii, which highlights the importance of structurally diverse capsular polysaccharide in the virulence of this bacterium.
CARBOHYDRATE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Christine M. Harvey, Katherine H. O'Toole, Chunliang Liu, Patrick Mariano, Debra Dunaway-Mariano, Karen N. Allen
Article
Biochemistry & Molecular Biology
Margarita A. Tararina, Katie K. Dam, Manaswni Dhingra, Kim D. Janda, Bruce A. Palfey, Karen N. Allen
Summary: The research elucidated the mechanism of NicA2, showing its preference for oxidizing tertiary amines with an efficient reductive half-reaction and very slow oxidative half-reaction, suggesting that the true oxidizing agent is unknown.
Article
Multidisciplinary Sciences
Katherine H. O'Toole, Barbara Imperiali, Karen N. Allen
Summary: The monoPGT superfamily is characterized by high diversity among its members, with frequent fusion with other pathway members. Phylogenetic reconstruction reveals a burst of functionalization within the superfamily, with a minority of members containing only the minimal PGT catalytic domain. The commonality of fusion partners in the monoPGT superfamily suggests advantageous colocalization of pathway members at membrane interfaces.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Paula C. Ortet, Samantha N. Muellers, Lauren A. Viarengo-Baker, Kristina Streu, Blair R. Szymczyna, Aaron B. Beeler, Karen N. Allen, Adrian Whitty
Summary: Research shows that the binding affinity of Nrf2 for KEAP1 can be replicated in a cyclic 7-mer peptide, achieved through optimizing the conformation of the cyclic compound; Analysis using X-ray crystal structures and machine learning indicates that strain locations in the bound ligand can be identified by observing patterns of subangstrom distortions; Optimizing the cyclic peptide affinity is driven by conformational preorganization associated with specific substitutions and geometries, as well as by reducing strain in the ETGE motif.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Yuping Liu, Siting Pan, Xinshuai Zhang, Hua Huang
Summary: Pantothenic acid is converted to beta-alanine and (R)-pantoate, and then (R)-pantoate is transformed to aldopentoate in a reconstituted pathway identified through genomic enzymology strategy. The pathway genes, common in Proteobacterial genomes, are responsible for the biodegradation of pantothenic acid.
ACS CHEMICAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Katherine H. O'Toole, Hannah M. Bernstein, Karen N. Allen, Barbara Imperiali
Summary: Phosphoglycosyl transferases (PGTs) are essential for the initiation of complex glycoconjugate biosynthesis pathways and recent research has revealed two unique superfamilies of PGT enzymes. Studies on PGTs have been challenging due to their integral membrane nature but exciting new information on their structures and mechanisms has been derived. The two superfamilies, polyPGT and monoPGT, may initiate different pathways within the same organism and have distinct modes of catalysis.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Chemistry, Medicinal
Lewis D. Turner, Alexander L. Nielsen, Lucy Lin, Antonio J. Campedelli, Nicholas R. Silvaggi, Jason S. Chen, Amanda E. Wakefield, Karen N. Allen, Kim D. Janda
Summary: When designing small-molecule inhibitors for the A serotype of botulinum neurotoxins, it is important to consider the flexibility and morphological changes of the light chain, as well as the impact of inhibitor enantioselectivity and active-site morphology.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Yongxin Li, Hua Huang, Xinshuai Zhang
Summary: This study discovered the catabolic pathway of sorbitol and its 1-deoxy analogue and experimentally verified the responsible gene cluster. Furthermore, the conservation of this catabolic gene cluster was observed in most members of the Firmicutes phylum.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Karen N. Allen, Christian P. Whitman
Summary: Enzymes are categorized into superfamilies based on sequence, structural, and mechanistic similarities, with profound evolutionary implications. The potential power of mechanistically diverse superfamilies to identify common ancestry, predict function, and specify specificity was demonstrated in a 1996 paper by Babbitt et al. The outcomes of genomic enzymology approach have gone beyond functional assignment, providing fundamental insights into enzyme evolution through the study of superfamilies.
Article
Chemistry, Physical
Qiongxiang Yan, Hua Huang, Xinshuai Zhang
Summary: This study elucidates the chemical steps of the ergothioneine sulfonate catabolic pathway and demonstrates its full pathway reconstitution. Additionally, it reveals the presence of the ergothioneine sulfonate pathway in various bacterial species.
Article
Biochemistry & Molecular Biology
Samantha N. Muellers, Mattias M. Nyitray, Nicholas Reynarowych, Edina Saljanin, Annie Laurie Benzie, Alan R. Schoenfeld, Brian J. Stockman, Karen N. Allen
Summary: The study reports the structure and function of the enzyme AGNH in Trichomonas vaginalis, which is associated with purine nucleoside specificity. Through X-ray crystal structure analysis, residue Asp231 responsible for the uncommon specificity of AGNH was identified, and its role led to changes in substrate binding pose and the repositioning of the His80 acid/base catalyst in the protein structure.
Article
Biochemistry & Molecular Biology
Samantha N. Muellers, Margarita A. Tararina, Uros Kuzmanovic, James E. Galagan, Karen N. Allen
Summary: This article reports the biophysical and structural properties of a bacterial monoamine oxidase (caMAO) from Corynebacterium ammoniagenes. caMAO catalyzes the oxidation of a range of monoamine substrates including dopamine and norepinephrine. The study reveals that the catalytic activity of caMAO is regulated by an unusual cysteine residue (Cys424) in its active site. Structural analysis also identifies the conservation of a secondary substrate inhibition site in related proteins of the same superfamily. The analysis of caMAO in the context of the FAO superfamily suggests potential roles for these bacterial MAOs in monoamine and polyamine degradation and catabolic pathways related to nitrogen scavenging.
Review
Biochemistry & Molecular Biology
Hayley L. Knox, Karen N. Allen
Summary: The use of protein sequences in genomic enzymology has led to significant advances in understanding enzyme structure, mechanism, and function. This approach enables the identification of new substrates, metabolites, and reaction mechanisms through bioinformatic tools. Studying enzyme superfamilies holistically provides insights into enzyme evolution and the diversity of their substrates and mechanisms.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alyssa J. J. Anderson, Greg J. J. Dodge, Karen N. N. Allen, Barbara Imperiali
Summary: In this study, the C-terminus of a prototypic monoPGT was structurally characterized for the first time, revealing that 19 C-terminal residues play a significant structural role in a subset of monoPGTs. This new structural information enabled the identification of co-conserved sequence fingerprints that predict NDP-sugar substrate specificity for this subset of monoPGTs. A Hidden Markov model was generated to assign the substrate of previously unannotated monoPGTs accurately.
Article
Biochemistry & Molecular Biology
Samantha N. Muellers, Mattias M. Nyitray, Nicholas Reynarowych, Edina Saljanin, Annie Laurie Benzie, Alan R. Schoenfeld, Brian J. Stockman, Karen N. Allen
Summary: This study reports the crystal structures of an important enzyme involved in the pathogenesis of Trichomonas vaginalis. The structures reveal unique substrate specificity and identify key residues responsible for this specificity. These findings have important implications for understanding the mechanism of trichomoniasis and developing related drugs.