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PDBsum entry 1mar
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Oxidoreductase(NADP)
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PDB id
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1mar
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References listed in PDB file
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Key reference
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Title
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Refined 1.8 a structure of human aldose reductase complexed with the potent inhibitor zopolrestat.
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Authors
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D.K.Wilson,
I.Tarle,
J.M.Petrash,
F.A.Quiocho.
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Ref.
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Proc Natl Acad Sci U S A, 1993,
90,
9847-9851.
[DOI no: ]
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PubMed id
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Abstract
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As the action of aldose reductase (EC 1.1.1.21) is believed to be linked to the
pathogenesis of diabetic complications affecting the nervous, renal, and visual
systems, the development of therapeutic agents has attracted intense effort. We
report the refined 1.8 A x-ray structure of the human holoenzyme complexed with
zopolrestat, one of the most potent noncompetitive inhibitors. The zopolrestat
fits snugly in the hydrophobic active site pocket and induces a hinge-flap
motion of two peptide segments that closes the pocket. Excellent complementarity
and affinity are achieved on inhibitor binding by the formation of 110 contacts
(< or = 4 A) with 15 residues (10 hydrophobic), 13 with the NADPH coenzyme
and 9 with four water molecules. The structure is key to understanding the mode
of action of this class of inhibitors and for rational design of better
therapeutics.
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Secondary reference #1
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Title
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An unlikely sugar substrate site in the 1.65 a structure of the human aldose reductase holoenzyme implicated in diabetic complications.
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Authors
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D.K.Wilson,
K.M.Bohren,
K.H.Gabbay,
F.A.Quiocho.
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Ref.
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Science, 1992,
257,
81-84.
[DOI no: ]
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PubMed id
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Headers
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