1ads
From Proteopedia
(New page: 200px<br /> <applet load="1ads" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ads, resolution 1.65Å" /> '''AN UNLIKELY SUGAR S...) |
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caption="1ads, resolution 1.65Å" /> | caption="1ads, resolution 1.65Å" /> | ||
'''AN UNLIKELY SUGAR SUBSTRATE SITE IN THE 1.65 ANGSTROMS STRUCTURE OF THE HUMAN ALDOSE REDUCTASE HOLOENZYME IMPLICATED IN DIABETIC COMPLICATIONS'''<br /> | '''AN UNLIKELY SUGAR SUBSTRATE SITE IN THE 1.65 ANGSTROMS STRUCTURE OF THE HUMAN ALDOSE REDUCTASE HOLOENZYME IMPLICATED IN DIABETIC COMPLICATIONS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Aldose reductase, which catalyzes the reduced form of nicotinamide adenine | + | 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== | ==About this Structure== | ||
| - | 1ADS 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 NAP as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1ADS 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=NAP:'>NAP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1ADS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Quiocho, F | + | [[Category: Quiocho, F A.]] |
| - | [[Category: Wilson, D | + | [[Category: Wilson, D K.]] |
[[Category: NAP]] | [[Category: NAP]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:43:22 2008'' |
Revision as of 09:43, 21 February 2008
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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
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 with as ligand. Active as Aldehyde reductase, with EC number 1.1.1.21 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
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