2pd5: Difference between revisions
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<StructureSection load='2pd5' size='340' side='right' caption='[[2pd5]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='2pd5' size='340' side='right' caption='[[2pd5]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2pd5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2pd5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PD5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PD5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZST:3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE+ACETIC+ACID'>ZST</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZST:3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE+ACETIC+ACID'>ZST</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hvn|2hvn]], [[2pd9|2pd9]], [[2pdb|2pdb]], [[2pdc|2pdc]], [[2pdf|2pdf]], [[2pdg|2pdg]], [[2pdh|2pdh]], [[2pdi|2pdi]], [[2pdj|2pdj]], [[2pdk|2pdk]], [[2pdl|2pdl]], [[2pdm|2pdm]], [[2pdn|2pdn]], [[2pdp|2pdp]], [[2pdq|2pdq]], [[2pdu|2pdu]], [[2pdw|2pdw]], [[2pdx|2pdx]], [[2pdy|2pdy]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hvn|2hvn]], [[2pd9|2pd9]], [[2pdb|2pdb]], [[2pdc|2pdc]], [[2pdf|2pdf]], [[2pdg|2pdg]], [[2pdh|2pdh]], [[2pdi|2pdi]], [[2pdj|2pdj]], [[2pdk|2pdk]], [[2pdl|2pdl]], [[2pdm|2pdm]], [[2pdn|2pdn]], [[2pdp|2pdp]], [[2pdq|2pdq]], [[2pdu|2pdu]], [[2pdw|2pdw]], [[2pdx|2pdx]], [[2pdy|2pdy]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=2pd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pd5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pd5 RCSB], [http://www.ebi.ac.uk/pdbsum/2pd5 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=2pd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pd5 OCA], [http://pdbe.org/2pd5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pd5 RCSB], [http://www.ebi.ac.uk/pdbsum/2pd5 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2pd5" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Aldehyde reductase]] | [[Category: Aldehyde reductase]] | ||
[[Category: | [[Category: Human]] | ||
[[Category: Heine, A]] | [[Category: Heine, A]] | ||
[[Category: Klebe, G]] | [[Category: Klebe, G]] | ||
Revision as of 03:42, 10 September 2015
Human aldose reductase mutant V47I complexed with zopolrestatHuman aldose reductase mutant V47I complexed with zopolrestat
Structural highlights
Function[ALDR_HUMAN] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies. 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 PubMedInhibition of human aldose reductase (ALR2) evolved as a promising therapeutic concept to prevent late complications of diabetes. As well as appropriate affinity and bioavailability, putative inhibitors should possess a high level of selectivity for ALR2 over the related aldehyde reductase (ALR1). We investigated the selectivity-determining features by gradually mapping the residues deviating between the binding pockets of ALR1 and ALR2 into the ALR2 binding pocket. The resulting mutational constructs of ALR2 (eight point mutations and one double mutant) were probed for their influence towards ligand selectivity by X-ray structure analysis of the corresponding complexes and isothermal titration calorimetry (ITC). The binding properties of these mutants were evaluated using a ligand set of zopolrestat, a related uracil derivative, IDD388, IDD393, sorbinil, fidarestat and tolrestat. Our study revealed induced-fit adaptations within the mutated binding site as an essential prerequisite for ligand accommodation related to the selectivity discrimination of the ligands. However, our study also highlights the limits of the present understanding of protein-ligand interactions. Interestingly, binding site mutations not involved in any direct interaction to the ligands in various cases show significant effects towards their binding thermodynamics. Furthermore, our results suggest the binding site residues deviating between ALR1 and ALR2 influence ligand affinity in a complex interplay, presumably involving changes of dynamic properties and differences of the solvation/desolvation balance upon ligand binding. Merging the binding sites of aldose and aldehyde reductase for detection of inhibitor selectivity-determining features.,Steuber H, Heine A, Podjarny A, Klebe G J Mol Biol. 2008 Jun 20;379(5):991-1016. Epub 2008 Apr 8. PMID:18495158[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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