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 |
- 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
-
A Multicenter Prospective Hospital-based Cohort Study on the Efficacy and Safety of Pitavastatin
Current Diabetes Reviews Sex Impact on Biomarkers, Pharmacokinetics and Pharmacodynamics
Current Medicinal Chemistry Inhibitors of Steroidal Cytochrome P450 Enzymes as Targets for Drug Development
Recent Patents on Anti-Cancer Drug Discovery Highlights on Important Medicinal Plants for the Menopause Syndrome
Current Women`s Health Reviews Natriuretic Peptide Family: New Aspects
Current Medicinal Chemistry - Cardiovascular & Hematological Agents New Advances in the Field of Calcium Channel Antagonists: Cardiovascular Effects and Structure-Activity Relationships
Current Medicinal Chemistry - Cardiovascular & Hematological Agents The Synthetic Cannabinoids Phenomenon
Current Pharmaceutical Design Flow-Injection Potentiometric Method for the Routine Determination of Chloride: Application to Bread Analysis
Current Analytical Chemistry Editorial (Thematic Issue: G-protein Coupled Receptors in Vascular Biology: Implication in Health and Disease)
Current Vascular Pharmacology Potential Phytotherapeutic Approaches for the Treatment of Alzheimer’s Disease: An Overview
Current Traditional Medicine Mechanisms of Dexamethasone-Induced Hypertension
Current Hypertension Reviews Potential Role of Hydrogen Sulfide in the Pathogenesis of Vascular Dysfunction in Septic Shock
Current Vascular Pharmacology Neutralization of Interleukin-1β Reduces Vasospasm and Alters Cerebral Blood Vessel Density Following Experimental Subarachnoid Hemorrhage in Rats
Current Neurovascular Research EDITORIAL: “The Faces of Mania: The Legacy of Athanasios Koukopoulos”
Current Neuropharmacology <i>Nigella sativa</i> – A Functional Spice From A Pharaoh’s Tomb to Modern Healthcare
The Natural Products Journal Endothelial Nitric Oxide Synthase Gene Therapy for Erectile Dysfunction
Current Pharmaceutical Design L-Arginine Signalling Potential in the Brain: The Peripheral Gets Central
Recent Patents on CNS Drug Discovery (Discontinued) Complications of Anti-Vascular Endothelial Growth Factor Drugs
Current Drug Therapy New Insights into Adipokines as Potential Biomarkers for Type-2 Diabetes Mellitus
Current Medicinal Chemistry The Role of Anticoagulation in IPF
Current Respiratory Medicine Reviews