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PDBsum entry 1ef3
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Oxidoreductase
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PDB id
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1ef3
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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M.Oka,
Y.Matsumoto,
S.Sugiyama,
N.Tsuruta,
M.Matsushima.
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Ref.
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J Med Chem, 2000,
43,
2479-2483.
[DOI no: ]
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PubMed id
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Abstract
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The absolute configuration of the aldose reductase (AR) inhibitor,
(+)-(2S,4S)-6-fluoro-2',5'-dioxospiro¿chroman-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¿chroman-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.
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