2f2k
From Proteopedia
(New page: 200px<br /> <applet load="2f2k" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f2k, resolution 1.94Å" /> '''Aldose reductase te...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2f2k.gif|left|200px]]<br /> | + | [[Image:2f2k.gif|left|200px]]<br /><applet load="2f2k" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2f2k" size=" | + | |
caption="2f2k, resolution 1.94Å" /> | caption="2f2k, resolution 1.94Å" /> | ||
'''Aldose reductase tertiary complex with NADPH and DEG'''<br /> | '''Aldose reductase tertiary complex with NADPH and DEG'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Aldose reductase (AR) is a monomeric NADPH-dependent oxidoreductase that | + | 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 conformation and interactions of DCEG with AR were consistent with our previously published molecular dynamics model of glutathionyl-propanal binding to AR. The current structure identifies major interactions of glutathione conjugates with the AR active-site residues. |
==About this Structure== | ==About this Structure== | ||
| - | 2F2K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NDP and TGG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] Full crystallographic information is available from [http:// | + | 2F2K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=TGG:'>TGG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F2K OCA]. |
==Reference== | ==Reference== | ||
| Line 16: | Line 15: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bhatnagar, A.]] | [[Category: Bhatnagar, A.]] | ||
| - | [[Category: Petrash, J | + | [[Category: Petrash, J M.]] |
| - | [[Category: Ramana, K | + | [[Category: Ramana, K V.]] |
[[Category: Singh, R.]] | [[Category: Singh, R.]] | ||
| - | [[Category: Srivastava, S | + | [[Category: Srivastava, S K.]] |
| - | [[Category: Watowich, S | + | [[Category: Watowich, S J.]] |
| - | [[Category: White, M | + | [[Category: White, M A.]] |
[[Category: NDP]] | [[Category: NDP]] | ||
[[Category: TGG]] | [[Category: TGG]] | ||
| Line 29: | Line 28: | ||
[[Category: tertiary complex]] | [[Category: tertiary complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:07 2008'' |
Revision as of 15:17, 21 February 2008
|
Aldose reductase tertiary complex with NADPH and DEG
Overview
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 conformation and interactions of DCEG with AR were consistent with our previously published molecular dynamics model of glutathionyl-propanal binding to AR. The current structure identifies major interactions of glutathione conjugates with the AR active-site residues.
About this Structure
2F2K is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Aldehyde reductase, with EC number 1.1.1.21 Full crystallographic information is available from OCA.
Reference
Structure of a glutathione conjugate bound to the active site of aldose reductase., Singh R, White MA, Ramana KV, Petrash JM, Watowich SJ, Bhatnagar A, Srivastava SK, Proteins. 2006 Jul 1;64(1):101-10. PMID:16639747
Page seeded by OCA on Thu Feb 21 17:17:07 2008
