2iq0: Difference between revisions
New page: left|200px<br /> <applet load="2iq0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2iq0, resolution 1.95Å" /> '''Crystal Structure o... |
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[[Image:2iq0.gif|left|200px]]<br /> | [[Image:2iq0.gif|left|200px]]<br /><applet load="2iq0" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2iq0, resolution 1.95Å" /> | caption="2iq0, resolution 1.95Å" /> | ||
'''Crystal Structure of Aldose Reductase complexed with Hexanoic Acid'''<br /> | '''Crystal Structure of Aldose Reductase complexed with Hexanoic Acid'''<br /> | ||
==Overview== | ==Overview== | ||
The competitive inhibition constants of series of inhibitors related to | 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== | ==About this Structure== | ||
2IQ0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAP and 6NA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 2IQ0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAP:'>NAP</scene> and <scene name='pdbligand=6NA:'>6NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IQ0 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Brownlee, J | [[Category: Brownlee, J M.]] | ||
[[Category: Harrison, D | [[Category: Harrison, D H.T.]] | ||
[[Category: 6NA]] | [[Category: 6NA]] | ||
[[Category: NAP]] | [[Category: NAP]] | ||
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[[Category: tim-barrel]] | [[Category: tim-barrel]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:55:01 2008'' | ||
Revision as of 18:55, 21 February 2008
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Crystal Structure of Aldose Reductase complexed with Hexanoic 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
2IQ0 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Aldehyde reductase, with EC number 1.1.1.21 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
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