Abstract
Aminoacyl-tRNA synthetase:transfer RNA (aaRS:tRNA) systems became recently essential targets in molecular medicine, because perturbed recognition of cognate tRNAs by aaRSs and poor precision in tRNA aminoacylation do not guarantee accurate protein biosynthesis, thus leading to diseases. Sets of identity determinants situated at particular zones of tRNA are responsible for functional accuracy. Recent work in X-ray crystallography has revealed various snapshots of aaRS:ligand complexes which represent the stages required for aminoacylation. Here we focus on a small group of class I aaRSs conserved in evolution, the ArgRSs, GluRSs, GlnRSs, and atypical LysRSs found mostly in Archaea and in a few Bacteria, that catalyze amino acid activation only in the presence of their cognate tRNAs. Structural and functional features of these aaRSs, ranked in subclass Ib, together with their peculiar mode of tRNA recognition and identity expression are reviewed and compared. Strategies to inhibit class Ib aaRS:tRNA aminoacylation systems, their dysfunction leading to human diseases, and the implications for pharmacology are outlined.
Keywords: Aminoacylation, tRNA, Aminoacyl-tRNA synthetase and diseases, Aminoacyl-tRNA synthetase as drug target, Protein-biomolecule interactions, tRNA, tRNA identity determinants.
Current Topics in Medicinal Chemistry
Title:Interplay between Catalysts and Substrates for Activity of Class Ib Aminoacyl-tRNA Synthetases and Implications for Pharmacology
Volume: 16 Issue: 6
Author(s): Preyesh Stephen, Sheng-Xiang Lin and Richard Giegé
Affiliation:
Keywords: Aminoacylation, tRNA, Aminoacyl-tRNA synthetase and diseases, Aminoacyl-tRNA synthetase as drug target, Protein-biomolecule interactions, tRNA, tRNA identity determinants.
Abstract: Aminoacyl-tRNA synthetase:transfer RNA (aaRS:tRNA) systems became recently essential targets in molecular medicine, because perturbed recognition of cognate tRNAs by aaRSs and poor precision in tRNA aminoacylation do not guarantee accurate protein biosynthesis, thus leading to diseases. Sets of identity determinants situated at particular zones of tRNA are responsible for functional accuracy. Recent work in X-ray crystallography has revealed various snapshots of aaRS:ligand complexes which represent the stages required for aminoacylation. Here we focus on a small group of class I aaRSs conserved in evolution, the ArgRSs, GluRSs, GlnRSs, and atypical LysRSs found mostly in Archaea and in a few Bacteria, that catalyze amino acid activation only in the presence of their cognate tRNAs. Structural and functional features of these aaRSs, ranked in subclass Ib, together with their peculiar mode of tRNA recognition and identity expression are reviewed and compared. Strategies to inhibit class Ib aaRS:tRNA aminoacylation systems, their dysfunction leading to human diseases, and the implications for pharmacology are outlined.
Export Options
About this article
Cite this article as:
Stephen Preyesh, Lin Sheng-Xiang and Giegé Richard, Interplay between Catalysts and Substrates for Activity of Class Ib Aminoacyl-tRNA Synthetases and Implications for Pharmacology, Current Topics in Medicinal Chemistry 2016; 16 (6) . https://dx.doi.org/10.2174/1568026615666150819110018
DOI https://dx.doi.org/10.2174/1568026615666150819110018 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Disease Progression in Children with Vertically-Acquired HIV Infection in Sub-Saharan Africa: Reviewing the Need for HIV Treatment
Current HIV Research Viruses and Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets “Vascular Incontinence” and Normal-Pressure Hydrocephalus: Two Commonsources of Elderly Incontinence with Brain Etiologies
Current Drug Therapy Emerging Therapies in Relapsing-Remitting Multiple Sclerosis
Reviews on Recent Clinical Trials Vascular Pharmacotherapy and Dementia
Current Vascular Pharmacology Sorafenib Decreases Extrahepatic Collaterals in Hepatocellular Carcinoma: Implication of the Synergistic Effect of Sorafenib and Transcatheter Chemoembolization
Current Medical Imaging Experimental Rodent Models of Vascular Dementia: A Systematic Review
CNS & Neurological Disorders - Drug Targets Role of COL4A1 in Basement-Membrane Integrity and Cerebral Small-Vessel Disease. The COL4A1 Stroke Syndrome
Current Medicinal Chemistry Phosphonomethoxyalkyl Analogs of Nucleotides
Current Pharmaceutical Design HIV-1-Associated Dementia During HAART Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Matrix Metalloproteinases as Potential Targets in the Venous Dilation Associated with Varicose Veins
Current Drug Targets Ideational Fluency in Patients with Rheumatoid Arthritis
Current Rheumatology Reviews Hsp70 Molecular Chaperones: Emerging Roles in Human Disease and Identification of Small Molecule Modulators
Current Topics in Medicinal Chemistry Neuro-AIDS: Current Status and Challenges to Antiretroviral Drug Therapy (ART) for Its Treatment
Current Drug Therapy Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review
Current Neuropharmacology Regulation of Angiogenesis by the Small Heat Shock Protein αB-Crystallin
Current Angiogenesis (Discontinued) Molecular Targets of Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued) Immunopathology of Brucella Infection
Recent Patents on Anti-Infective Drug Discovery Cerebral Vascular Aging: Extending the Concept of Pulse Wave Encephalopathy Through Capillaries to the Cerebral Veins
Current Aging Science Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach
Current Neuropharmacology