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3h4g

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Revision as of 05:59, 7 December 2018

Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity

Structural highlights

3h4g is a 1 chain structure with sequence from Sus scrofa. This structure supersedes the now removed PDB entry 2ao0. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1pwm, 3cv7
Activity:	Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AK1A1_PIG] Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Structure determination of porcine aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat was carried out to explain the difference in the potency of the inhibitor for aldose and aldehyde reductases. The hydrogen bonds between the active-site residues Tyr50, His113, and Trp114 and fidarestat are conserved in the two enzymes. In aldose reductase, Leu300 forms a hydrogen bond through its main-chain nitrogen atom with the exocyclic amide group of the inhibitor, which when replaced with a Pro in aldehyde reductase, cannot form a hydrogen bond, thus causing a loss in binding energy. Furthermore, in aldehyde reductase, the side chain of Trp220 occupies a disordered split conformation that is not observed in aldose reductase. Molecular modeling and inhibitory activity measurements suggest that the difference in the interaction between the side chain of Trp220 and fidarestat may contribute to the difference in the binding of the inhibitor to the enzymes.

Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity.,El-Kabbani O, Carbone V, Darmanin C, Oka M, Mitschler A, Podjarny A, Schulze-Briese C, Chung RP J Med Chem. 2005 Aug 25;48(17):5536-42. PMID:16107153^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ El-Kabbani O, Carbone V, Darmanin C, Oka M, Mitschler A, Podjarny A, Schulze-Briese C, Chung RP. Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity. J Med Chem. 2005 Aug 25;48(17):5536-42. PMID:16107153 doi:10.1021/jm050412o

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3h4g"

@@ Line 1: / Line 1: @@
 ==Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity==
 <StructureSection load='3h4g' size='340' side='right' caption='[[3h4g]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pwm|1pwm]], [[3cv7|3cv7]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3h4g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h4g OCA], [http://pdbe.org/3h4g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3h4g RCSB], [http://www.ebi.ac.uk/pdbsum/3h4g PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3h4g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h4g OCA], [http://pdbe.org/3h4g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3h4g RCSB], [http://www.ebi.ac.uk/pdbsum/3h4g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3h4g ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h4/3h4g_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h4/3h4g_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

3h4g

From Proteopedia

Revision as of 05:59, 7 December 2018

Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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