1x98: Difference between revisions
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|PDB= 1x98 |SIZE=350|CAPTION= <scene name='initialview01'>1x98</scene>, resolution 1.30Å | |PDB= 1x98 |SIZE=350|CAPTION= <scene name='initialview01'>1x98</scene>, resolution 1.30Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene> and <scene name='pdbligand=FIS:(2S,4R)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4 | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene> and <scene name='pdbligand=FIS:(2S,4R)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE'>FIS</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= [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= | |GENE= | ||
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[[Category: the c-terminal end of the barrel]] | [[Category: the c-terminal end of the barrel]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 14:11:27 2008'' | ||
Revision as of 15:11, 23 March 2008
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| , resolution 1.30Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | Aldehyde reductase, with EC number 1.1.1.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Aldose Reductase complexed with 2S4R (Stereoisomer of Fidarestat, 2S4S)
OverviewOverview
Structure determinations of human aldose reductase holoenzyme in complex with the 2S4R-,2R4S- and 2R4R-isomers of the potent inhibitor Fidarestat ((2S,4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazoline]-2-carboxamide ) were carried out in order to elucidate the binding modes responsible for the differences in their inhibitory potencies. In the complex structure with the 2R4S-isomer the cyclic imide moiety formed hydrogen bonds with the side-chains of Trp111, Tyr48 and His110. In the attempt to determine the complex structure with the least potent 2R4R-isomer this ligand was not observed, and instead, the active site was simultaneously occupied by two citrate molecules (occupancies of 60% and 40%). In the case of 2S4R, the active site was occupied by a citrate molecule which anchors the 2S4R-isomer from its carbamoyl group. The structures of the complexes suggest that the differences in the interactions between the cyclic imide rings and carbamoyl groups of the compounds with residues His110, Trp111, Trp219 and Cys298 account for differences in their inhibitory potencies.
About this StructureAbout this Structure
1X98 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat: stereospecific interaction between the enzyme and a cyclic imide type inhibitor., El-Kabbani O, Darmanin C, Oka M, Schulze-Briese C, Tomizaki T, Hazemann I, Mitschler A, Podjarny A, J Med Chem. 2004 Aug 26;47(18):4530-7. PMID:15317464
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