Abstract
The NADPH-dependent reduction of glucose reaction that is catalyzed by Aldose Reductase (AR) follows a sequential ordered kinetic mechanism in which the co-factor NADPH binds to the enzyme prior to the aldehyde substrate. The kinetic/structural experiments have found a conformational change involving a hinge-like movement of a surface loop (residues 213-224) which is anticipated to take place upon the binding of the diphosphate moiety of NADPH. The reorientation of this loop, expected to permit the release of NADP+, represents the rate-limiting step of the catalytic mechanism. This study reveals: 1) The Translation/Libration/Screw (TLS) analysis of absolute B-factors of apo AR crystal structures indicates that the 212-224 loop might move as a rigid group. 2) Residues that make the flexible loop slide in the AR binary and ternary complexes. 3) The normalized B-factors separate this segment into three differnt clusters with fewer residues.
Keywords: Aldo-keto reductase, B-factor, clustering, crystal structure, statistical analysis, structural dynamics, TLS.
Graphical Abstract
Current Proteomics
Title:B-factor Analysis and Conformational Rearrangement of Aldose Reductase
Volume: 11 Issue: 3
Author(s): Ganesaratnam K. Balendiran, J. Rajendran Pandian, Evin Drake, Anubhav Vinayak, Malkhey Verma and Duilio Cascio
Affiliation:
Keywords: Aldo-keto reductase, B-factor, clustering, crystal structure, statistical analysis, structural dynamics, TLS.
Abstract: The NADPH-dependent reduction of glucose reaction that is catalyzed by Aldose Reductase (AR) follows a sequential ordered kinetic mechanism in which the co-factor NADPH binds to the enzyme prior to the aldehyde substrate. The kinetic/structural experiments have found a conformational change involving a hinge-like movement of a surface loop (residues 213-224) which is anticipated to take place upon the binding of the diphosphate moiety of NADPH. The reorientation of this loop, expected to permit the release of NADP+, represents the rate-limiting step of the catalytic mechanism. This study reveals: 1) The Translation/Libration/Screw (TLS) analysis of absolute B-factors of apo AR crystal structures indicates that the 212-224 loop might move as a rigid group. 2) Residues that make the flexible loop slide in the AR binary and ternary complexes. 3) The normalized B-factors separate this segment into three differnt clusters with fewer residues.
Export Options
About this article
Cite this article as:
Balendiran K. Ganesaratnam, Pandian Rajendran J., Drake Evin, Vinayak Anubhav, Verma Malkhey and Cascio Duilio, B-factor Analysis and Conformational Rearrangement of Aldose Reductase, Current Proteomics 2014; 11 (3) . https://dx.doi.org/10.2174/157016461103140922163444
DOI https://dx.doi.org/10.2174/157016461103140922163444 |
Print ISSN 1570-1646 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6247 |
- 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
Related Articles
-
Management of Glia-Mediated Neuroinflammation and Related Patents
Recent Patents on Inflammation & Allergy Drug Discovery Preclinical Safety and Pharmacokinetic Profile of 3K3A-APC, a Novel, Modified Activated Protein C for Ischemic Stroke
Current Pharmaceutical Design Therapeutic Approach for Neuronal Disease by Regulating Reninangiotensin System
Current Hypertension Reviews Neurobiology of Sleep Disturbances in Neurodegenerative Disorders
Current Pharmaceutical Design Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers
Current Alzheimer Research One Special Question to Start with: Can HIF/NFkB be a Target in Inflammation?
Endocrine, Metabolic & Immune Disorders - Drug Targets Pros and Cons of Aggressive Blood Pressure Lowering in Patients with Type 2 Diabetes
Current Vascular Pharmacology The NMDA Receptor/Ion Channel Complex: A Drug Target for Modulating Synaptic Plasticity and Excitotoxicity
Current Pharmaceutical Design The Mammalian Tachykinin Ligand-Receptor System: An Emerging Target for Central Neurological Disorders
CNS & Neurological Disorders - Drug Targets Cannabis sativa L. Constituents and Their Role in Neuroinflammation
Current Bioactive Compounds Consideration of a Pharmacological Combinatorial Approach to Inhibit Chronic Inflammation in Alzheimer’s Disease
Current Alzheimer Research Clinical Management of Diabetes Mellitus in the Older Adult Patient
Current Diabetes Reviews Nanoparticle-Mediated Drug Delivery: Blood-Brain Barrier as the Main Obstacle to Treating Infectious Diseases in CNS
Current Pharmaceutical Design Spin Trapping: An Essential Tool for the Study of Diseases Caused by Oxidative Stress
Current Topics in Medicinal Chemistry Glycolytic Inhibition and Antidiabetic Activity on Synthesized Flavanone Scaffolds with Computer Aided Drug Designing Tools
Letters in Drug Design & Discovery Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology Natural Animal Models of Neurodegenerative Protein Misfolding Diseases
Current Pharmaceutical Design Renal Endothelial Dysfunction in Diabetic Nephropathy
Cardiovascular & Hematological Disorders-Drug Targets p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Decoding Common Features of Neurodegenerative Disorders: From Differentially Expressed Genes to Pathways
Current Genomics