☆ 4.8 Article

An asymmetric structure of bacterial TrpRS supports the half-of-the-sites catalytic mechanism and facilitates antimicrobial screening

NUCLEIC ACIDS RESEARCH (2023)

相关参考文献

注意：仅列出部分参考文献，下载原文获取全部文献信息。

Article Biochemistry & Molecular Biology

Investigate Natural Product Indolmycin and the Synthetically Improved Analogue Toward Antimycobacterial Agents

Yuhong Yang et al.

Summary: Indolmycin (IND) is a microbial natural product that selectively inhibits bacterial tryptophanyl-tRNA synthetase (TrpRS). IND shows promising antibacterial activity against Mycobacterium tuberculosis (Mtb), especially the 4''-methylated compound Y-13. The cocrystal structure of Mtb TrpRS complexed with IND and ATP reveals that IND can affect the activity of TrpRS and has synergistic effects with other antibacterial agents, potentially leading to the development of new antibiotics.

ACS CHEMICAL BIOLOGY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structural insights into the specific interaction between Geobacillus stearothermophilus tryptophanyl-tRNA synthetase and antimicrobial Chuangxinmycin

Shuai Fan et al.

Summary: The interaction mechanism between the antimicrobial compound CXM and the bacterial enzyme TrpRS has been elucidated using X-ray crystallography and molecular dynamics simulations. This study provides insights for the screening and design of more effective CXM analogs against both Gram-negative and Gram-positive bacteria.

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

添加到收藏夹

Review Pharmacology & Pharmacy

Prospects of halofuginone as an antiprotozoal drug scaffold

Jasmita Gill et al.

Summary: Halofuginone, derived from a Chinese herb, has shown beneficial effects in treating various diseases such as parasitic diseases, cancer, fibrosis, and autoimmune disorders. Its mechanism of action involves inhibiting the prolyl-tRNA synthetase enzyme for its antiparasitic role.

DRUG DISCOVERY TODAY (2022)

添加到收藏夹

Review Oncology

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

Hidekatsu Nakai et al.

Summary: With the development of poly(ADP-ribose) polymerase inhibitors, the treatment of advanced ovarian cancer is undergoing significant changes. This review aims to provide guidance for individualized treatment based on the mechanism of action of molecularly targeted drugs currently used in Japan. The importance of achieving complete surgery for cure in ovarian cancer treatment and the need for individualized use of bevacizumab, olaparib, and niraparib are emphasized through the analysis of relevant data.

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY (2022)

添加到收藏夹

Article Chemistry, Medicinal

Design, Synthesis, and Proof-of-Concept of Triple-Site Inhibitors against Aminoacyl-tRNA Synthetases

Zhengjun Cai et al.

Summary: This study reports the design of a new class of triple-site aaRS inhibitors by targeting a specific enzyme. The inhibitors successfully compete with all three substrates, blocking the essential enzymatic activity involved in protein translation. The compounds also demonstrate potent antibacterial activity.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Fragment screening and structural analyses highlight the ATP-assisted ligand binding for inhibitor discovery against type 1 methionyl-tRNA synthetase

Jia Yi et al.

Summary: Methionyl-tRNA synthetase (MetRS) is an essential enzyme that charges tRNA(Met) with l-methionine (L-Met) to decode the ATG codon for protein translation. Crystal structures of a representative MetRS1 from Staphylococcus aureus (SaMetRS) were reported, revealing differences in structural organization and dynamic movement compared to human cytosolic MetRS (HcMetRS, or MetRS2). Screening of chemical fragments against SaMetRS identified ten hits that bound to either the L-Met binding site or an auxiliary pocket near the tRNA binding site. Interestingly, fragment binding was enhanced by ATP in most cases, suggesting a potential ATP-assisted ligand binding mechanism in MetRS1. The findings inspire the development of new MetRS1 inhibitors for fighting microbial infections.

NUCLEIC ACIDS RESEARCH (2022)

添加到收藏夹

Review Biochemistry & Molecular Biology

Functional and pathologic association of aminoacyl-tRNA synthetases with cancer

Yulseung Sung et al.

Summary: Aminoacyl-tRNA synthetases (ARSs) have been found to play a significant role in tumorigenesis, making them potential targets for cancer detection, prevention, and treatment.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

添加到收藏夹

Review Biochemistry & Molecular Biology

Aminoacyl-tRNA synthetases in Charcot-Marie-Tooth disease: A gain or a loss?

Han Zhang et al.

Summary: Charcot-Marie-Tooth disease (CMT) is a common inherited neurodegenerative disorder with an increasing number of identified CMT-associated variants as causative factors. Recent studies have shown that in CMT, variants of Aminoacyl-tRNA synthetases (aaRS) can lead to toxic gain-of-function, and not all variants are due to the loss of aminoacylation activity. Researching the functions of these CMT-related AaRS variants is crucial for understanding the pathogenesis of CMT.

JOURNAL OF NEUROCHEMISTRY (2021)

添加到收藏夹

Review Biochemistry & Molecular Biology

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

Luping Pang et al.

Summary: Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in all three kingdoms of life, and have been recognized as suitable targets for small molecule anti-infectives. This review discusses the catalytic activities of aaRSs, inhibitory mechanisms, and species-selectivity determinants of reported inhibitors. The structural perspective highlights opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

添加到收藏夹

Article Multidisciplinary Sciences

Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase

Bingyi Chen et al.

Summary: Reveromycin A (RM-A) selectively inhibits eukaryotic cytoplasmic isoleucyltRNA synthetase (IleRS). The co-crystal structure suggests that RM-A molecule occupies the tRNA(Ile) binding site of Saccharomyces cerevisiae IleRS, and that RM-A cooperates with isoleucine or isoleucyl-adenylate for IleRS binding.

NATURE COMMUNICATIONS (2021)

添加到收藏夹

Review Genetics & Heredity

Drosophila Models for Charcot-Marie-Tooth Neuropathy Related to Aminoacyl-tRNA Synthetases

Laura Morant et al.

Summary: CMT is a common neuromuscular disorder, with aaRS mutations causing different subtypes and similar clinical manifestations. Drosophila models are valuable for studying the molecular pathways of CMT and testing candidate drugs.

GENES (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

X-shaped structure of bacterial heterotetrameric tRNA synthetase suggests cryptic prokaryote functions and a rationale for synthetase classifications

Yingchen Ju et al.

Summary: AaRSs, specifically GlyRSs, exhibit unique structures with heterotetrameric composition, while EcGlyRS's X-shaped structure suggests pressure to avoid single polypeptide format. The unique five-domain beta-subunit plays diverse roles in alpha-subunit binding, ATP coordination, and tRNA recognition, contributing to a better understanding of ancient enzyme families. EcGlyRS's architecture aligns with a model for the emergence of two classes of tRNA synthetases.

NUCLEIC ACIDS RESEARCH (2021)

添加到收藏夹

Article Multidisciplinary Sciences

tRNA overexpression rescues peripheral neuropathy caused by mutations in tRNA synthetase

Amila Zuko et al.

Summary: Heterozygous mutations in six transfer RNA synthetase genes cause Charcot-Marie-Tooth peripheral neuropathy. Mutant tRNA synthetases in CMT inhibit protein synthesis by binding tRNA(Gly) but failing to release it, leading to tRNAGly sequestration and ribosome stalling. Overexpression of tRNA(Gly) rescues protein synthesis, peripheral neuropathy, and ISR activation, suggesting therapeutic potential in CMT2D.

SCIENCE (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

X-shaped structure of bacterial heterotetrameric tRNA synthetase suggests cryptic prokaryote functions and a rationale for synthetase classifications

Yingchen Ju et al.

Summary: AaRSs (aminoacyl-tRNA synthetases) are divided into two classes throughout evolution, with the heterotetrameric GlyRS from Escherichia coli having a unique structure where its alpha and beta polypeptides cannot be replaced by a single chain. The unprecedented X-shaped structure of EcGlyRS sheds light on the ancient enzyme family and its functions, contributing to a better understanding of this essential protein.

NUCLEIC ACIDS RESEARCH (2021)

添加到收藏夹

Article Cardiac & Cardiovascular Systems

Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis

Jiangbin Wu et al.

CIRCULATION RESEARCH (2020)

添加到收藏夹

Article Microbiology

First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment

David Tenero et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2019)

添加到收藏夹

Review Biotechnology & Applied Microbiology

Aminoacyl-tRNA synthetases as therapeutic targets

Nam Hoon Kwon et al.

NATURE REVIEWS DRUG DISCOVERY (2019)

添加到收藏夹

Article Multidisciplinary Sciences

Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy

Sven Bervoets et al.

NATURE COMMUNICATIONS (2019)

添加到收藏夹

Review Biochemistry & Molecular Biology

Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases

Na Wei et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

添加到收藏夹

Review Biochemistry & Molecular Biology

Part-of-the-sites binding and reactivity in the homooligomeric enzymes - facts and artifacts

Beata Wielgus-Kutrowska et al.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Identification of an auxiliary druggable pocket in the DNA gyrase ATPase domain using fragment probes

Xiaojie Huang et al.

MEDCHEMCOMM (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Selective Inhibition of Bacterial Tryptophanyl-tRNA Synthetases by Indolmycin Is Mechanism-based

Tishan L. Williams et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2016)

添加到收藏夹

Review Biotechnology & Applied Microbiology

Twenty years on: the impact of fragments on drug discovery

Daniel A. Erlanson et al.

NATURE REVIEWS DRUG DISCOVERY (2016)

添加到收藏夹

Article Multidisciplinary Sciences

CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

Weiwei He et al.

NATURE (2015)

添加到收藏夹

Review Medicine, Research & Experimental

Aminoacyl-tRNA synthetases in medicine and disease

Peng Yao et al.

EMBO MOLECULAR MEDICINE (2013)

添加到收藏夹

Article Multidisciplinary Sciences

ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase

Huihao Zhou et al.

NATURE (2013)

添加到收藏夹

Article Biochemical Research Methods

Structure of the prolyl-tRNA synthetase from the eukaryotic pathogen Giardia lamblia

Eric T. Larson et al.

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2012)

添加到收藏夹

Article Biochemical Research Methods

DoGSiteScorer: a web server for automatic binding site prediction, analysis and druggability assessment

Andrea Volkamer et al.

BIOINFORMATICS (2012)

添加到收藏夹

Article Biochemical Research Methods

Molecular replacement with MOLREP

Alexei Vagin et al.

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

添加到收藏夹

Article Biochemical Research Methods

MolProbity: all-atom structure validation for macromolecular crystallography

Vincent B. Chen et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2010)

添加到收藏夹

Article Biochemical Research Methods

XDS

Wolfgang Kabsch

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

添加到收藏夹

Article Biochemical Research Methods

Features and development of Coot

P. Emsley et al.

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

添加到收藏夹

Article Biochemical Research Methods

Structure of a tryptophanyl-tRNA synthetase containing an iron-sulfur cluster

Gye Won Han et al.

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS (2010)

添加到收藏夹

Article Biochemistry & Molecular Biology

2.9 Å crystal structure of ligand-free tryptophanyl-tRNA synthetase: Domain movements fragment the adenine nucleotide binding site

Valentin A. Ilyin et al.

PROTEIN SCIENCE (2010)

添加到收藏夹

Article Microbiology

A Novel Tryptophanyl-tRNA Synthetase Gene Confers High-Level Resistance to Indolmycin

James J. Vecchione et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2009)

添加到收藏夹

Article Biochemistry & Molecular Biology

Asymmetric Amino Acid Activation by Class II Histidyl-tRNA Synthetase from Escherichia coli

Ethan Guth et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

添加到收藏夹

Article Biochemistry & Molecular Biology

Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states

Ning Shen et al.

NUCLEIC ACIDS RESEARCH (2008)

添加到收藏夹

Article Multidisciplinary Sciences

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site

Fernando L. Rock et al.

SCIENCE (2007)

添加到收藏夹

Article Biochemistry & Molecular Biology

Crystal structure of tryptophanyl-tRNA synthetase complexed with adenosine-5′ tetraphosphate:: Evidence for distributed use of catalytic binding energy in amino acid activation by class I aminoacyl-tRNA synthetases

Pascal Retailleau et al.

JOURNAL OF MOLECULAR BIOLOGY (2007)

添加到收藏夹

Article Biochemical Research Methods

The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability

Frank H. Niesen et al.

NATURE PROTOCOLS (2007)

添加到收藏夹

Article Biochemistry & Molecular Biology

Two conformations of a crystalline human tRNA synthetase-tRNA complex:: implications for protein synthesis

Xiang-Lei Yang et al.

EMBO JOURNAL (2006)

添加到收藏夹

Article Multidisciplinary Sciences

Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts

JT Woo et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2006)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structure of human tryptophanyl-tRNA synthetase in complex with tRNA(Trp) reveals the molecular basis of tRNA recognition and specificity

Ning Shen et al.

NUCLEIC ACIDS RESEARCH (2006)

添加到收藏夹

Article Biochemistry & Molecular Biology

Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment - Insights into substrate recognition, tRNA binding, and angiogenesis activity

YD Yu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2004)

添加到收藏夹

Article Biochemistry & Molecular Biology

Residues Lys-149 and Glu-153 switch the aminoacylation of tRNATrp in Bacillus subtilis

J Jia et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2004)

添加到收藏夹

Article Biochemistry & Molecular Biology

Fluorescence based structural analysis of tryptophan analogue-AMP formation in single tryptophan mutants of Bacillus stearothermophilus tryptophanyl-tRNA synthetase

M Acchione et al.

BIOCHEMISTRY (2003)

添加到收藏夹

Article Multidisciplinary Sciences

Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains

XL Yang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

添加到收藏夹

Article Biochemistry & Molecular Biology

Interconversion of ATP binding and conformational free energies by tryptophanyl-tRNA synthetase: Structures of ATP bound to open and closed, pre-transition-state conformations

P Retailleau et al.

JOURNAL OF MOLECULAR BIOLOGY (2003)

添加到收藏夹

Article Biochemistry & Molecular Biology

Two essential regions for tRNA recognition in Bacillus subtilis tryptophanyl-tRNA synthetase

J Jia et al.

BIOCHEMICAL JOURNAL (2002)

添加到收藏夹

Article Biochemistry & Molecular Biology

Class I tyrosyl-tRNA synthetase has a class II mode of cognate tRNA recognition

A Yaremchuk et al.

EMBO JOURNAL (2002)

添加到收藏夹

Article Biochemical Research Methods

High-density miniaturized thermal shift assays as a general strategy for drug discovery

MW Pantoliano et al.

JOURNAL OF BIOMOLECULAR SCREENING (2001)

添加到收藏夹

© Peeref 2019-2024. All rights reserved.