2ipw
From Proteopedia
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| - | [[Image:2ipw.gif|left|200px]] | + | [[Image:2ipw.gif|left|200px]] |
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| - | '''Crystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acid''' | + | {{Structure |
| + | |PDB= 2ipw |SIZE=350|CAPTION= <scene name='initialview01'>2ipw</scene>, resolution 2.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <scene name='pdbligand=2CL:(2,6-DICHLOROPHENYL)ACETIC ACID'>2CL</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= AKR1B1, ALDR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acid''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2IPW is a [ | + | 2IPW 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=2IPW OCA]. |
==Reference== | ==Reference== | ||
| - | Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes., Brownlee JM, Carlson E, Milne AC, Pape E, Harrison DH, Bioorg Chem. 2006 Dec;34(6):424-44. Epub 2006 Nov 2. PMID:[http:// | + | Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes., Brownlee JM, Carlson E, Milne AC, Pape E, Harrison DH, Bioorg Chem. 2006 Dec;34(6):424-44. Epub 2006 Nov 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17083960 17083960] |
[[Category: Aldehyde reductase]] | [[Category: Aldehyde reductase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: tim-barrel]] | [[Category: tim-barrel]] | ||
| - | ''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 17:32:16 2008'' |
Revision as of 15:32, 20 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | AKR1B1, ALDR1 (Homo sapiens) | ||||||
| Activity: | Aldehyde reductase, with EC number 1.1.1.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acid
Overview
The competitive inhibition constants of series of inhibitors related to phenylacetic acid against both wild-type and the doubly mutanted C298A/W219Y aldose reductase have been measured. Van't Hoff analysis shows that these acids bind with an enthalpy near -6.8 kcal/mol derived from the electrostatic interactions, while the 100-fold differences in binding affinity appear to be largely due to entropic factors that result from differences in conformational freedom in the unbound state. These temperature studies also point out the difference between substrate and inhibitor binding. X-ray crystallographic analysis of a few of these inhibitor complexes both confirms the importance of a previously described anion binding site and reveals the hydrophobic nature of the primary binding site and its general plasticity. Based on these results, N-glycylthiosuccinimides were synthesized to demonstrate their potential in studies that probe distal binding sites. Reduced alpha-lipoic acid, an anti-oxidant and therapeutic for diabetic complications, was shown to bind aldose reductase with a binding constant of 1 microM.
About this Structure
2IPW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes., Brownlee JM, Carlson E, Milne AC, Pape E, Harrison DH, Bioorg Chem. 2006 Dec;34(6):424-44. Epub 2006 Nov 2. PMID:17083960
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