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[[Image:1ads.gif|left|200px]]
[[Image:1ads.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1ads |SIZE=350|CAPTION= <scene name='initialview01'>1ads</scene>, resolution 1.65&Aring;
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The line below this paragraph, containing "STRUCTURE_1ads", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1ads| PDB=1ads | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ads FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ads OCA], [http://www.ebi.ac.uk/pdbsum/1ads PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ads RCSB]</span>
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}}
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'''AN UNLIKELY SUGAR SUBSTRATE SITE IN THE 1.65 ANGSTROMS STRUCTURE OF THE HUMAN ALDOSE REDUCTASE HOLOENZYME IMPLICATED IN DIABETIC COMPLICATIONS'''
'''AN UNLIKELY SUGAR SUBSTRATE SITE IN THE 1.65 ANGSTROMS STRUCTURE OF THE HUMAN ALDOSE REDUCTASE HOLOENZYME IMPLICATED IN DIABETIC COMPLICATIONS'''
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[[Category: Quiocho, F A.]]
[[Category: Quiocho, F A.]]
[[Category: Wilson, D K.]]
[[Category: Wilson, D K.]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:08:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:38:15 2008''
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Revision as of 07:08, 2 May 2008

Image:1ads.gif

Template:STRUCTURE 1ads

AN UNLIKELY SUGAR SUBSTRATE SITE IN THE 1.65 ANGSTROMS STRUCTURE OF THE HUMAN ALDOSE REDUCTASE HOLOENZYME IMPLICATED IN DIABETIC COMPLICATIONS


Overview

Aldose reductase, which catalyzes the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of a wide variety of aromatic and aliphatic carbonyl compounds, is implicated in the development of diabetic and galactosemic complications involving the lens, retina, nerves, and kidney. A 1.65 angstrom refined structure of a recombinant human placenta aldose reductase reveals that the enzyme contains a parallel beta 8/alpha 8-barrel motif and establishes a new motif for NADP-binding oxidoreductases. The substrate-binding site is located in a large, deep elliptical pocket at the COOH-terminal end of the beta barrel with a bound NADPH in an extended conformation. The highly hydrophobic nature of the active site pocket greatly favors aromatic and apolar substrates over highly polar monosaccharides. The structure should allow for the rational design of specific inhibitors that might provide molecular understanding of the catalytic mechanism, as well as possible therapeutic agents.

About this Structure

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

Reference

An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications., Wilson DK, Bohren KM, Gabbay KH, Quiocho FA, Science. 1992 Jul 3;257(5066):81-4. PMID:1621098 Page seeded by OCA on Fri May 2 10:08:17 2008

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