1ae4
From Proteopedia
(New page: 200px<br /><applet load="1ae4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ae4, resolution 2.40Å" /> '''ALDEHYDE REDUCTASE C...) |
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| - | [[Image:1ae4.gif|left|200px]]<br /><applet load="1ae4" size=" | + | [[Image:1ae4.gif|left|200px]]<br /><applet load="1ae4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ae4, resolution 2.40Å" /> | caption="1ae4, resolution 2.40Å" /> | ||
'''ALDEHYDE REDUCTASE COMPLEXED WITH COFACTOR AND INHIBITOR, ALPHA CARBON ATOMS ONLY'''<br /> | '''ALDEHYDE REDUCTASE COMPLEXED WITH COFACTOR AND INHIBITOR, ALPHA CARBON ATOMS ONLY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Aldehyde reductase is an enzyme capable of metabolizing a wide variety of | + | Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The tertiary structures of aldehyde reductase and aldose reductase are similar and consist of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. We have determined the X-ray crystal structure of porcine aldehyde reductase holoenzyme in complex with an aldose reductase inhibitor, tolrestat, at 2.4 A resolution to obtain a picture of the binding conformation of inhibitors to aldehyde reductase. Tolrestat binds in the active site pocket of aldehyde reductase and interacts through van der Waals contacts with Arg 312 and Asp 313. The carboxylate group of tolrestat is within hydrogen bonding distance with His 113 and Trp 114. Mutation of Arg 312 to alanine in porcine aldehyde reductase alters the potency of inhibition of the enzyme by aldose reductase inhibitors. Our results indicate that the structure of the inhibitor-binding site of aldehyde reductase differs from that of aldose reductase due to the participation of nonconserved residues in its formation. A major difference is the participation of Arg 312 and Asp 313 in lining the inhibitor-binding site in aldehyde reductase but not in aldose reductase. |
==About this Structure== | ==About this Structure== | ||
| - | 1AE4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with NAP and TOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] Full crystallographic information is available from [http:// | + | 1AE4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=NAP:'>NAP</scene> and <scene name='pdbligand=TOL:'>TOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AE4 OCA]. |
==Reference== | ==Reference== | ||
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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 11:43:30 2008'' |
Revision as of 09:43, 21 February 2008
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ALDEHYDE REDUCTASE COMPLEXED WITH COFACTOR AND INHIBITOR, ALPHA CARBON ATOMS ONLY
Overview
Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The tertiary structures of aldehyde reductase and aldose reductase are similar and consist of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. We have determined the X-ray crystal structure of porcine aldehyde reductase holoenzyme in complex with an aldose reductase inhibitor, tolrestat, at 2.4 A resolution to obtain a picture of the binding conformation of inhibitors to aldehyde reductase. Tolrestat binds in the active site pocket of aldehyde reductase and interacts through van der Waals contacts with Arg 312 and Asp 313. The carboxylate group of tolrestat is within hydrogen bonding distance with His 113 and Trp 114. Mutation of Arg 312 to alanine in porcine aldehyde reductase alters the potency of inhibition of the enzyme by aldose reductase inhibitors. Our results indicate that the structure of the inhibitor-binding site of aldehyde reductase differs from that of aldose reductase due to the participation of nonconserved residues in its formation. A major difference is the participation of Arg 312 and Asp 313 in lining the inhibitor-binding site in aldehyde reductase but not in aldose reductase.
About this Structure
1AE4 is a Single protein structure of sequence from Sus scrofa with and as ligands. Active as Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 Full crystallographic information is available from OCA.
Reference
Studies on the inhibitor-binding site of porcine aldehyde reductase: crystal structure of the holoenzyme-inhibitor ternary complex., el-Kabbani O, Carper DA, McGowan MH, Devedjiev Y, Rees-Milton KJ, Flynn TG, Proteins. 1997 Oct;29(2):186-92. PMID:9329083
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