creators_name: Sekhon, Gurprit
creators_name: Singh, Balvinder
creators_name: Singh, Ranvir
type: article
datestamp: 2022-03-28 10:20:00
lastmod: 2022-03-28 10:20:00
metadata_visibility: show
title: Role of Cys-298 in specific recognition of glutathione by aldose reductase
ispublished: pub
subjects: QR
keywords: Aldose reductase; diabetes; glutathione; molecular dynamics; polyol pathway
note: Copyright of this article belongs to OPEN ACCESS
abstract: Aldose reductase (AR) is an NADPH-dependent oxidoreductase that is well-studied for its role in Diabetes Mellitus. Glutathione conjugated aldehydes are efficiently catalysed by AR. We have employed molecular dynamics simulations to investigate the dynamics of a glutathione analog, γ-glutamyl-S-(1,2-di-carboxyethyl)-cysteinyl-glycine (DCEG), into the binding pocket of AR. Study revealed that backbone nitrogens of Ala-299 and Leu-300 form a tiny pocket gated by thiol group of Cys-298. The glycine moiety of DCEG was able to displace the thiol group of Cys-298 to make hydrogen bond interactions with backbone of Ala-299, Leu-300, and Leu-301. This study provides the details of the dynamic interactions of DCEG in the binding pocket of AR, and shall aid in the design/discovery of differential inhibitors against AR.Communicated by Ramaswamy H. Sarma.
date: 2021-02-25
date_type: published
publication: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
pagerange: 1-9
refereed: TRUE
official_url: https://pubmed.ncbi.nlm.nih.gov/33627036/
citation:   Sekhon, Gurprit and Singh, Balvinder and Singh, Ranvir  (2021) Role of Cys-298 in specific recognition of glutathione by aldose reductase.  JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS.  pp. 1-9.