5ac0: Difference between revisions

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-'''Unreleased structure'''
-The entry 5ac0 is ON HOLD
+==ovis aries Aldehyde Dehydrogenase 1A1 in complex with a duocarmycin analog==
+<StructureSection load='5ac0' size='340' side='right'caption='[[5ac0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ac0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AC0 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=5ac0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ac0 OCA], [https://pdbe.org/5ac0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ac0 RCSB], [https://www.ebi.ac.uk/pdbsum/5ac0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ac0 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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.
-Authors: Koch, M.F., Harteis, S., Blank, I.D., Pestel, G., Tietze, L.F., Ochsenfeld, C., Schneider, S., Sieber, S.A.
+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>
-Description: ovis aries Aldehyde Dehydrogenase 1A1 in complex with a duocarmycin analog
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Pestel, G]]
+<div class="pdbe-citations 5ac0" style="background-color:#fffaf0;"></div>
-[[Category: Sieber, S.A]]
-[[Category: Tietze, L.F]]
+==See Also==
-[[Category: Schneider, S]]
+*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
-[[Category: Harteis, S]]
+== References ==
-[[Category: Blank, I.D]]
+<references/>
-[[Category: Koch, M.F]]
+__TOC__
-[[Category: Ochsenfeld, C]]
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Ovis aries]]
+[[Category: Blank ID]]
+[[Category: Harteis S]]
+[[Category: Koch MF]]
+[[Category: Ochsenfeld C]]
+[[Category: Pestel G]]
+[[Category: Schneider S]]
+[[Category: Sieber SA]]
+[[Category: Tietze LF]]