5abm: Difference between revisions
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''' | ==Sheep aldehyde dehydrogenase 1A1== | ||
<StructureSection load='5abm' size='340' side='right' caption='[[5abm]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5abm]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ABM FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TXE:[[(2R,3S,4R,5R)-5-[(3R)-3-AMINOCARBONYL-3,4-DIHYDRO-2H-PYRIDIN-1-YL]-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANIDYL-PHOSPHORYL]+[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHYL+PHOSPHATE'>TXE</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ac0|5ac0]], [[5ac1|5ac1]], [[5ac2|5ac2]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Retinal_dehydrogenase Retinal dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.36 1.2.1.36] </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=5abm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5abm OCA], [http://pdbe.org/5abm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5abm RCSB], [http://www.ebi.ac.uk/pdbsum/5abm PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/AL1A1_SHEEP AL1A1_SHEEP]] Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial pi-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. | |||
Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.,Koch MF, Harteis S, Blank ID, Pestel G, Tietze LF, Ochsenfeld C, Schneider S, Sieber SA Angew Chem Int Ed Engl. 2015 Sep 16. doi: 10.1002/anie.201505749. PMID:26373694<ref>PMID:26373694</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5abm" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Retinal dehydrogenase]] | |||
[[Category: Blank, I D]] | |||
[[Category: Harteis, S]] | |||
[[Category: Koch, M F]] | |||
[[Category: Ochsenfeld, C]] | |||
[[Category: Pestel, G]] | [[Category: Pestel, G]] | ||
[[Category: Schneider, S]] | [[Category: Schneider, S]] | ||
[[Category: | [[Category: Sieber, S A]] | ||
[[Category: | [[Category: Tietze, L F]] | ||
[[Category: | [[Category: Activity]] | ||
[[Category: | [[Category: Oxidation-reduction process]] | ||
[[Category: Oxidoreductase]] | |||
Revision as of 11:04, 30 September 2015
Sheep aldehyde dehydrogenase 1A1Sheep aldehyde dehydrogenase 1A1
Structural highlights
Function[AL1A1_SHEEP] Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid. Publication Abstract from PubMedAnalogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial pi-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.,Koch MF, Harteis S, Blank ID, Pestel G, Tietze LF, Ochsenfeld C, Schneider S, Sieber SA Angew Chem Int Ed Engl. 2015 Sep 16. doi: 10.1002/anie.201505749. PMID:26373694[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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