1mar: Difference between revisions
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[[Image:1mar.gif|left|200px]] | [[Image:1mar.gif|left|200px]] | ||
'''REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT''' | {{Structure | ||
|PDB= 1mar |SIZE=350|CAPTION= <scene name='initialview01'>1mar</scene>, resolution 1.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=ZST:3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE ACETIC ACID'>ZST</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] | |||
|GENE= | |||
}} | |||
'''REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1MAR is a [ | 1MAR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MAR OCA]. | ||
==Reference== | ==Reference== | ||
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat., Wilson DK, Tarle I, Petrash JM, Quiocho FA, Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51. PMID:[http:// | Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat., Wilson DK, Tarle I, Petrash JM, Quiocho FA, Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8234324 8234324] | ||
[[Category: Aldehyde reductase]] | [[Category: Aldehyde reductase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: oxidoreductase(nadp)]] | [[Category: oxidoreductase(nadp)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:41:06 2008'' | ||
Revision as of 13:41, 20 March 2008
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| , resolution 1.8Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Aldehyde reductase, with EC number 1.1.1.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT
OverviewOverview
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.
About this StructureAbout this Structure
1MAR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat., Wilson DK, Tarle I, Petrash JM, Quiocho FA, Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51. PMID:8234324
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