3ld5: Difference between revisions
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==Human aldose reductase mutant T113S complexed with IDD594== | ==Human aldose reductase mutant T113S complexed with IDD594== | ||
<StructureSection load='3ld5' size='340' side='right' caption='[[3ld5]], [[Resolution|resolution]] 1.27Å' scene=''> | <StructureSection load='3ld5' size='340' side='right'caption='[[3ld5]], [[Resolution|resolution]] 1.27Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ld5]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3ld5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LD5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=LDT:IDD594'>LDT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=LDT:IDD594'>LDT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1us0|1us0]], [[3lbo|3lbo]], [[3lqg|3lqg]], [[3lep|3lep]], [[3lz3|3lz3]], [[3m4h|3m4h]], [[3lql|3lql]], [[3lz5|3lz5]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1us0|1us0]], [[3lbo|3lbo]], [[3lqg|3lqg]], [[3lep|3lep]], [[3lz3|3lz3]], [[3m4h|3m4h]], [[3lql|3lql]], [[3lz5|3lz5]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alr2 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alr2 ([https://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'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ld5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ld5 OCA], [https://pdbe.org/3ld5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ld5 RCSB], [https://www.ebi.ac.uk/pdbsum/3ld5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ld5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/ALDR_HUMAN 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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Aldose | *[[Aldose reductase 3D structures|Aldose reductase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Aldehyde reductase]] | [[Category: Aldehyde reductase]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Heine, A]] | [[Category: Heine, A]] | ||
[[Category: Klebe, G]] | [[Category: Klebe, G]] | ||
Revision as of 16:39, 4 May 2022
Human aldose reductase mutant T113S complexed with IDD594Human aldose reductase mutant T113S complexed with IDD594
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. Publication Abstract from PubMedImprovements on the computational methods for affinity prediction from the structure of protein-ligand complexes require a better understanding of the nature of molecular interactions and biomolecular recognition principles. In the present contribution, the binding of two chemically closely related human aldose reductase inhibitors had been studied by high-resolution X-ray analysis (0.92-1.35 A) and isothermal titration calorimetry against a series of single-site mutants of the wild-type protein. A crucial threonine thought to be involved in a short bromine-to-oxygen halogen bond to the inhibitors in the wild type has been mutated to the structurally similar residues alanine, cysteine, serine and valine. Overall, structurally, the binding mode of the inhibitors is conserved; however, small but significant geometrical adaptations are observed as a consequence of the spatial and electronic changes at the mutation site. They involve the opening of a central bond angle and shifts in consequence of the lost or gained halogen bonds. Remarkably, the tiny structural changes are responded by partly strong modulation of the thermodynamic profiles. Even though the free energy of binding is maximally perturbed by only 7 kJ/mol, much stronger modulations and shifts in the enthalpy and entropy signatures are revealed, which indicate a pronounced enthalpy/entropy compensation. However, an explanatory correlation can be detected when facing these perturbances against the small structural changes. This also provides deeper insights into how single-site mutations can alter the selectivity profile of closely related ligands against a target protein. Tracing the detail: how mutations affect binding modes and thermodynamic signatures of closely related aldose reductase inhibitors.,Koch C, Heine A, Klebe G J Mol Biol. 2011 Mar 11;406(5):700-12. Epub 2010 Dec 23. PMID:21185307[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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