1ef3
From Proteopedia
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|PDB= 1ef3 |SIZE=350|CAPTION= <scene name='initialview01'>1ef3</scene>, resolution 2.8Å | |PDB= 1ef3 |SIZE=350|CAPTION= <scene name='initialview01'>1ef3</scene>, resolution 2.8Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=FID:(2S,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4 | + | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=FID:(2S,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE'>FID</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: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''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 11:38:54 2008'' |
Revision as of 09:38, 23 March 2008
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| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Aldehyde reductase, with EC number 1.1.1.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE
Overview
The absolute configuration of the aldose reductase (AR) inhibitor, (+)-(2S,4S)-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxamide (fidarestat), was established indirectly by single-crystal X-ray analysis of (+)-(2S, 4S)-8-bromo-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxylic acid (1). The crystal structure of human AR complexed with fidarestat was determined, and the specific inhibition activity was discussed on the basis of the three-dimensional interactions between them. The structure clarified that fidarestat was located in the active site by hydrophilic and hydrophobic interactions and that the carbamoyl group of fidarestat was a very effective substituent for affinity to AR and for selectivity between AR and aldehyde reductase (AHR). Explanations for the differences between the observed activities of fidarestat and its stereoisomer 2 were suggested by computer modeling.
About this Structure
1EF3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography., Oka M, Matsumoto Y, Sugiyama S, Tsuruta N, Matsushima M, J Med Chem. 2000 Jun 15;43(12):2479-83. PMID:10882376
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