Abstract
The knowledge derived from the three-dimensional structure of a macromolecular receptor either in the native form or in complex with different ligands has given new insights to the development of improved drug candidates contributing to the drug development pipeline. The structure-based drug design approach has been tested on a number of macromolecular targets implicated in various diseases such as hypertension, glaucoma, HIV and influenza. This approach has also been employed for the development of new antidiabetic agents targeting glycogen phosphorylase (GP), an enzyme that modulates glucose levels in blood circulation. The key role of x-ray protein crystallography in the structure-based inhibitor design process is presented by the case of rabbit muscle GP (RMGPb) that shares increased homology with the liver isoenzyme. The properties of the allosteric binding sites of RMGPb are revealed by filing the interactions formed upon binding of characteristic functional groups and documenting the changes induced in the residues lining the site of interest.
Keywords: SGlycogen phosphorylase, inhibitors, structure-based drug design, type 2 diabetes, x-ray crystallography, macromolecular receptor, drug development, hypertension, glaucoma
Current Medicinal Chemistry
Title: From Structure – Based to Knowledge – Based Drug Design Through X-Ray Protein Crystallography: Sketching Glycogen Phosphorylase Binding Sites
Volume: 18 Issue: 17
Author(s): E. D. Chrysina, A. Chajistamatiou and M. Chegkazi
Affiliation:
Keywords: SGlycogen phosphorylase, inhibitors, structure-based drug design, type 2 diabetes, x-ray crystallography, macromolecular receptor, drug development, hypertension, glaucoma
Abstract: The knowledge derived from the three-dimensional structure of a macromolecular receptor either in the native form or in complex with different ligands has given new insights to the development of improved drug candidates contributing to the drug development pipeline. The structure-based drug design approach has been tested on a number of macromolecular targets implicated in various diseases such as hypertension, glaucoma, HIV and influenza. This approach has also been employed for the development of new antidiabetic agents targeting glycogen phosphorylase (GP), an enzyme that modulates glucose levels in blood circulation. The key role of x-ray protein crystallography in the structure-based inhibitor design process is presented by the case of rabbit muscle GP (RMGPb) that shares increased homology with the liver isoenzyme. The properties of the allosteric binding sites of RMGPb are revealed by filing the interactions formed upon binding of characteristic functional groups and documenting the changes induced in the residues lining the site of interest.
Export Options
About this article
Cite this article as:
D. Chrysina E., Chajistamatiou A. and Chegkazi M., From Structure – Based to Knowledge – Based Drug Design Through X-Ray Protein Crystallography: Sketching Glycogen Phosphorylase Binding Sites, Current Medicinal Chemistry 2011; 18 (17) . https://dx.doi.org/10.2174/092986711795933632
DOI https://dx.doi.org/10.2174/092986711795933632 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- 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
-
Osteoporosis and its Association with Non-Gonadal Hormones Involved in Hypertension, Adiposity and Hyperglycaemia
Current Drug Targets Magnetic Resonance-Based Metabolomics for Understanding Neurological Disorders: Current Status and Statistical Considerations
Current Metabolomics Organic Cation Transporters: Physiology, Toxicology and Special Focus on Ethidium as a Novel Substrate
Current Drug Metabolism Interaction Between Genetic Polymorphisms in Renin-Angiotensin System (RAS) and Therapeutic Efficacy of RAS Blockade in IgA Nephropathy
Current Pharmacogenomics Treat to Target in Spondyloarthritis: The Time has Come
Current Rheumatology Reviews Low Baseline Urine Creatinine Excretion Rate Predicts Poor Outcomes among Critically Ill Acute Stroke Patients
Current Neurovascular Research New Perspectives on Acetaminophen
Current Cardiology Reviews Clinical Vignettes: Integrated Care of Cancer Patients by Oncologists and Cardiologists
Current Cardiology Reviews Effects of Kallistatin on Oxidative Stress and Inflammation on Renal Ischemia-Reperfusion Injury in Mice
Current Vascular Pharmacology Association of SORL1 Gene Variants with Hippocampal and Cerebral Atrophy and Alzheimer's Disease
Current Alzheimer Research Gender Differences in the Effects of Angiotensin Receptor Blockers on Cardiovascular Disease
Current Pharmaceutical Design Nanocrystalline ZnO: A Competent and Reusable Catalyst for the Preparation of Pharmacology Relevant Heterocycles in the Aqueous Medium
Current Green Chemistry Glutathione Modulation and Oxidative Stress in Human Liver Slices
Current Drug Discovery Technologies Cardiovascular and Antidipsogenic Effects of Nesfatin-1
Current Pharmaceutical Design Phytoestrogens: Implications in Neurovascular Research
Current Neurovascular Research Barriers to Risk Stratification Accuracy in Ischemic Heart Disease in Women: The Role of Non-Obstructive Coronary Artery Disease
Current Pharmaceutical Design How Internet Technology Can Improve the Quality of Care for Substance Use Disorders
Current Drug Abuse Reviews Phosphodiesterases (PDEs) from Snake Venoms: Therapeutic Applications
Protein & Peptide Letters Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
Current Signal Transduction Therapy Neuropeptide/Receptor Expression and Plasticity in Micturition Pathways
Current Pharmaceutical Design