1t41
From Proteopedia
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|PDB= 1t41 |SIZE=350|CAPTION= <scene name='initialview01'>1t41</scene>, resolution 1.05Å | |PDB= 1t41 |SIZE=350|CAPTION= <scene name='initialview01'>1t41</scene>, resolution 1.05Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=ID5:[5-FLUORO-2-({[(4,5,7-TRIFLUORO-1,3-BENZOTHIAZOL-2-YL)METHYL]AMINO}CARBONYL)PHENOXY]ACETIC+ACID'>ID5</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1t40|1T40]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t41 OCA], [http://www.ebi.ac.uk/pdbsum/1t41 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t41 RCSB]</span> | ||
}} | }} | ||
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[[Category: Ruiz, F.]] | [[Category: Ruiz, F.]] | ||
[[Category: Schneider, T.]] | [[Category: Schneider, T.]] | ||
| - | [[Category: ID5]] | ||
| - | [[Category: NAP]] | ||
[[Category: aldose reductase]] | [[Category: aldose reductase]] | ||
[[Category: atomic resolution]] | [[Category: atomic resolution]] | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:51:02 2008'' |
Revision as of 20:51, 30 March 2008
| |||||||
| , resolution 1.05Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Aldehyde reductase, with EC number 1.1.1.21 | ||||||
| Related: | 1T40
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human aldose reductase complexed with NADP and IDD552
Overview
The X-ray crystal structure of human aldose reductase (ALR2) in complex with the inhibitor IDD552 was determined using crystals obtained from two crystallization conditions with different pH values (pH 5 and 8). In both structures the charged carboxylic head of the inhibitor binds to the active site, making hydrogen-bond interactions with His110 and Tyr48 and electrostatic interactions with NADP+. There is an important difference between the two structures: the observation of a double conformation of the carboxylic acid moiety of the inhibitor at pH 8, with one water molecule interacting with the main configuration. This is the first time that a water molecule has been observed deep inside the ALR2 active site. Furthermore, in the configuration with the lower occupancy factor the difference electron-density map shows a clear peak (2.5sigma) for the H atom in the hydrogen bond between the inhibitor's carboxylic acid and the Tyr48 side-chain O atom. The position of this peak implies that this H atom is shared between both O atoms, indicating possible direct proton transfer from this residue to the inhibitor. This fact agrees with the model of the catalytic mechanism, in which the proton is donated by the Tyr48 hydroxyl to the substrate. These observations are useful both in drug design and in understanding the ALR2 mechanism.
About this Structure
1T41 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystallographic structure of the aldose reductase-IDD552 complex shows direct proton donation from tyrosine 48., Ruiz F, Hazemann I, Mitschler A, Joachimiak A, Schneider T, Karplus M, Podjarny A, Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1347-54. Epub 2004, Jul 21. PMID:15272156
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