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1abn

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{{STRUCTURE_1abn| PDB=1abn | SCENE= }}
{{STRUCTURE_1abn| PDB=1abn | SCENE= }}
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'''THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX'''
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===THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX===
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==Overview==
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Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a broad range of aldehydes, including glucose. Since aldose reductase has been strongly implicated in the development of the chronic complications of diabetes mellitus, much effort has been devoted to understanding the structure and mechanism of this enzyme, and many aldose reductase inhibitors have been developed as potential drugs for the treatment of these complications. We describe here the 2.75 A crystal structure of recombinant human aldose reductase (Cys-298 to Ser mutant) complexed with NADPH. This mutant displays unusual kinetic behavior characterized by high Km/high Vmax substrate kinetics and reduced sensitivity to certain aldose reductase inhibitors. The crystal structure revealed that the enzyme is a beta/alpha-barrel with the coenzyme-binding domain located at the carboxyl-terminal end of the parallel strands of the barrel. The enzyme undergoes a large conformational change upon binding NADPH which involves the reorientation of loop 7 to a position which appears to lock the coenzyme into place. NADPH is bound to aldose reductase in an unusual manner, more similar to FAD- rather than NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in the crystal structure.
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The line below this paragraph, {{ABSTRACT_PUBMED_1447221}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 1447221 is the PubMed ID number.
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{{ABSTRACT_PUBMED_1447221}}
==About this Structure==
==About this Structure==
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[[Category: Petrash, J M.]]
[[Category: Petrash, J M.]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:04:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:32:25 2008''

Revision as of 13:32, 30 June 2008

Image:1abn.png

Template:STRUCTURE 1abn

THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX

Template:ABSTRACT PUBMED 1447221

About this Structure

1ABN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The crystal structure of the aldose reductase.NADPH binary complex., Borhani DW, Harter TM, Petrash JM, J Biol Chem. 1992 Dec 5;267(34):24841-7. PMID:1447221

Page seeded by OCA on Mon Jun 30 16:32:25 2008

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