2iqd: Difference between revisions

Revision as of 07:46, 4 May 2008

Crystal Structure of Aldose Reductase complexed with Lipoic Acid

OverviewOverview

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 StructureAbout this Structure

2IQD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 07:46:22 2008

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OCA

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 [[Image:2iqd.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2iqd |SIZE=350|CAPTION= <scene name='initialview01'>2iqd</scene>, resolution 2.0&Aring;
+The line below this paragraph, containing "STRUCTURE_2iqd", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=LPA:LIPOIC+ACID'>LPA</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= AKR1B1, ALDR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2iqd|  PDB=2iqd  |  SCENE=  }}
-|RELATEDENTRY=[[2ine|2INE]], [[2inz|2INZ]], [[2iq0|2IQ0]], [[2ipw|2IPW]], [[2is7|2IS7]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iqd OCA], [http://www.ebi.ac.uk/pdbsum/2iqd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iqd RCSB]</span>
-}}
 '''Crystal Structure of Aldose Reductase complexed with Lipoic Acid'''
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 [[Category: Harrison, D H.T.]]
 [[Category: Pape, E.]]
-[[Category: aldo-keto reductase]]
+[[Category: Aldo-keto reductase]]
-[[Category: ari]]
+[[Category: Ari]]
-[[Category: lipoic]]
+[[Category: Lipoic]]
-[[Category: tim-barrel]]
+[[Category: Tim-barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:46:22 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:47:25 2008''