5ac2: Difference between revisions
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<StructureSection load='5ac2' size='340' side='right'caption='[[5ac2]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='5ac2' size='340' side='right'caption='[[5ac2]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ac2]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5ac2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AC2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K9P:1-[(1S)-1-METHYL-5-OXIDANYL-1,2-DIHYDROBENZO[E]INDOL-3-YL]HEXAN-1-ONE'>K9P</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- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K9P:1-[(1S)-1-METHYL-5-OXIDANYL-1,2-DIHYDROBENZO[E]INDOL-3-YL]HEXAN-1-ONE'>K9P</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-ph+osphoryl]+[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+phosphate'>TXE</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ac2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ac2 OCA], [https://pdbe.org/5ac2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ac2 RCSB], [https://www.ebi.ac.uk/pdbsum/5ac2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ac2 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/AL1A1_HUMAN AL1A1_HUMAN] Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Blank ID]] | |||
[[Category: Blank | [[Category: Harteis S]] | ||
[[Category: Harteis | [[Category: Koch MF]] | ||
[[Category: Koch | [[Category: Ochsenfeld C]] | ||
[[Category: Ochsenfeld | [[Category: Pestel G]] | ||
[[Category: Pestel | [[Category: Schneider S]] | ||
[[Category: Schneider | [[Category: Sieber SA]] | ||
[[Category: Sieber | [[Category: Tietze LF]] | ||
[[Category: Tietze | |||
Revision as of 07:50, 25 May 2023
human aldehyde dehydrogenase 1A1 with duocarmycin analoghuman aldehyde dehydrogenase 1A1 with duocarmycin analog
Structural highlights
FunctionAL1A1_HUMAN Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity). 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. See AlsoReferences
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