1az2: Difference between revisions
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[[Image:1az2.jpg|left|200px]] | [[Image:1az2.jpg|left|200px]] | ||
'''CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE''' | {{Structure | ||
|PDB= 1az2 |SIZE=350|CAPTION= <scene name='initialview01'>1az2</scene>, resolution 2.9Å | |||
|SITE= <scene name='pdbsite=ACT:Active+Site'>ACT</scene> | |||
|LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=CIT:CITRIC ACID'>CIT</scene> | |||
|ACTIVITY= [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] | |||
|GENE= ALR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1AZ2 is a [ | 1AZ2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AZ2 OCA]. | ||
==Reference== | ==Reference== | ||
The alrestatin double-decker: binding of two inhibitor molecules to human aldose reductase reveals a new specificity determinant., Harrison DH, Bohren KM, Petsko GA, Ringe D, Gabbay KH, Biochemistry. 1997 Dec 23;36(51):16134-40. PMID:[http:// | The alrestatin double-decker: binding of two inhibitor molecules to human aldose reductase reveals a new specificity determinant., Harrison DH, Bohren KM, Petsko GA, Ringe D, Gabbay KH, Biochemistry. 1997 Dec 23;36(51):16134-40. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9405046 9405046] | ||
[[Category: Aldehyde reductase]] | [[Category: Aldehyde reductase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:04:07 2008'' | ||
Revision as of 11:04, 20 March 2008
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| , resolution 2.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | and | ||||||
| Gene: | ALR2 (Homo sapiens) | ||||||
| Activity: | Aldehyde reductase, with EC number 1.1.1.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE
OverviewOverview
It is generally expected that only one inhibitor molecule will bind to an enzyme active site. In fact, specific drug design theories depend upon this assumption. Here, we report the binding of two molecules of an inhibitor to the same active site which we observed in the 1.8 A resolution structure of the drug Alrestatin bound to a mutant of human aldose reductase. The two molecules of Alrestatin bind to the active site in a stacked arrangement (a double-decker). This stack positions the carboxylic acid of one drug molecule near the NADP+ cofactor at a previously determined anion binding site and the carboxylic acid of the second drug molecule near the carboxy-terminal tail of the enzyme. We propose that interactions of inhibitors with the carboxy-terminal loop of aldose reductase are critical for the development of inhibitors that are able to discriminate between aldose reductase and other members of the aldo-keto reductase superfamily. This finding suggests a new direction for the introduction of specificity to aldose reductase-targeted drugs.
About this StructureAbout this Structure
1AZ2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The alrestatin double-decker: binding of two inhibitor molecules to human aldose reductase reveals a new specificity determinant., Harrison DH, Bohren KM, Petsko GA, Ringe D, Gabbay KH, Biochemistry. 1997 Dec 23;36(51):16134-40. PMID:9405046
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