Structure of a glutathione conjugate bound to the active site of aldose reductase

Proteins
Ranvir SinghSatish K Srivastava

Abstract

Aldose reductase (AR) is a monomeric NADPH-dependent oxidoreductase that catalyzes the reduction of aldehydes, ketones, and aldo-sugars. AR has been linked to the development of hyperglycemic injury and is a clinical target for the treatment of secondary diabetic complications. In addition to reducing glucose, AR is key regulator of cell signaling through it's reduction of aldehydes derived from lipoproteins and membrane phospholipids. AR catalyzes the reduction of glutathione conjugates of unsaturated aldehydes with higher catalytic efficiency than free aldehydes. The X-ray structure of human AR holoenzyme in complex with the glutathione analogue S-(1,2-dicarboxyethyl) glutathione (DCEG) was determined at a resolution of 1.94 A. The distal carboxylate group of DCEG's dicarboxyethyl moiety interacted with the conserved AR anion binding site residues Tyr48, His110, and Trp111. The bound DCEG's glutathione backbone adopted the low-energy Y-shape form. The C-terminal carboxylate of DCEG glutathione's glycine formed hydrogen bonds to Leu301 and Ser302, while the remaining interactions between DCEG and AR were hydrophobic, permitting significant flexibility of the AR and glutathione (GS) analogue interaction. The observed conformati...Continue Reading

References

Oct 1, 1992·Biochemical Medicine and Metabolic Biology·A Bhatnagar, S K Srivastava
Jan 2, 1989·European Journal of Biochemistry·P A KarplusG E Schulz
Apr 28, 1968·Journal of Molecular Biology·B W Matthews
Jun 1, 1983·European Journal of Biochemistry·O EppA Wendel
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·D K WilsonF A Quiocho
Dec 26, 1995·Biochemical and Biophysical Research Communications·S SrivastavaN H Ansari
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Oct 23, 1997·The Biochemical Journal·J M JezT M Penning
Apr 18, 1998·Nature Structural Biology·K BeckerP A Karplus
Jun 6, 1998·The Journal of Biological Chemistry·S SrivastavaA Bhatnagar
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Oct 8, 1998·Acta Crystallographica. Section D, Biological Crystallography·I J TickleD S Moss
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·J L SussmanE E Abola
Apr 9, 1999·The Journal of Clinical Investigation·H L RittnerC M Weyand
Sep 14, 1999·The American Journal of Medicine·G J Parry
Apr 15, 2000·The Journal of Biological Chemistry·B L DixitS K Srivastava
Apr 20, 2000·Acta Crystallographica. Section D, Biological Crystallography·V CalderoneA Podjarny
Jul 15, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·J RuefA Bhatnagar
Oct 4, 2000·Biochemistry·K V RamanaA Bhatnagar
Sep 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·C R KissingerD Bouzida
Jun 14, 2002·The Journal of Biological Chemistry·Kota V RamanaSatish K Srivastava
Aug 10, 2002·Circulation Research·Ken ShinmuraAruni Bhatnagar
Nov 28, 2002·JAMA : the Journal of the American Medical Association·Matthew J Sheetz, George L King
Jul 31, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kota V RamanaSatish K Srivastava
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Oct 7, 2004·The Journal of Biological Chemistry·Sanjay SrivastavaAruni Bhatnagar

❮ Previous
Next ❯

Citations

May 6, 2008·Acta Crystallographica. Section D, Biological Crystallography·Mark Andrew WhiteIrina A Pikuleva
May 28, 2013·Oxidative Medicine and Cellular Longevity·Umesh C S Yadav, Kota V Ramana
Apr 13, 2010·Expert Review of Clinical Immunology·Satish K Srivastava, Kota V Ramana
Oct 5, 2013·Expert Opinion on Drug Discovery·Maria ChatzopoulouVassilis J Demopoulos
Oct 25, 2008·Drug Metabolism Reviews·Oleg A BarskiAruni Bhatnagar
Mar 1, 2011·Chemico-biological Interactions·Satish K SrivastavaKota V Ramana
Nov 18, 2008·Chemico-biological Interactions·Hans-Jörg Martin, Edmund Maser
Mar 27, 2007·Free Radical Biology & Medicine·Kota V RamanaSatish K Srivastava
Oct 24, 2013·The Plant Journal : for Cell and Molecular Biology·Katharina GläserErwin Grill
Aug 19, 2015·Acta Pharmacologica Sinica·Hong ZhangXiao-peng Hu
Sep 26, 2009·The International Journal of Biochemistry & Cell Biology·Kota V Ramana, Satish K Srivastava
Jun 21, 2011·Biochimica Et Biophysica Acta·Cornelia KochGerhard Klebe
Sep 12, 2006·Structure·Andrew T RussoStanley J Watowich
Dec 2, 2018·Future Medicinal Chemistry·Magdaléna Májeková
Feb 15, 2019·Expert Opinion on Therapeutic Patents·Luca Quattrini, Concettina La Motta
May 7, 2011·Biomolecular Concepts·Kota V Ramana
Mar 19, 2019·Journal of Biomolecular Structure & Dynamics·Yunsong MuSi Luo
Aug 25, 2011·Journal of Synchrotron Radiation·Cornelia KochGerhard Klebe
Nov 30, 2019·Oxidative Medicine and Cellular Longevity·Himangshu Sonowal, Kota V Ramana
Oct 28, 2019·Antioxidants·Francesco BalestriRoberta Moschini
Feb 26, 2021·Journal of Biomolecular Structure & Dynamics·Gurprit SekhonRanvir Singh

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.