1az2

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[[Image:1az2.jpg|left|200px]]
[[Image:1az2.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1az2 |SIZE=350|CAPTION= <scene name='initialview01'>1az2</scene>, resolution 2.9&Aring;
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The line below this paragraph, containing "STRUCTURE_1az2", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=ACT:Active+Site'>ACT</scene>
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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=CIT:CITRIC+ACID'>CIT</scene>, <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= ALR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_1az2| PDB=1az2 | 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=1az2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1az2 OCA], [http://www.ebi.ac.uk/pdbsum/1az2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1az2 RCSB]</span>
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}}
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'''CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE'''
'''CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE'''
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[[Category: Petsko, G A.]]
[[Category: Petsko, G A.]]
[[Category: Ringe, D.]]
[[Category: Ringe, D.]]
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[[Category: aldo-keto reductase]]
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[[Category: Aldo-keto reductase]]
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[[Category: inhibitor binding]]
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[[Category: Inhibitor binding]]
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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 10:52:01 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:50:20 2008''
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Revision as of 07:52, 2 May 2008

Image:1az2.jpg

Template:STRUCTURE 1az2

CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE


Overview

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 Structure

1AZ2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

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:9405046 Page seeded by OCA on Fri May 2 10:52:01 2008

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