6dum: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 3: / Line 3: @@
 <StructureSection load='6dum' size='340' side='right'caption='[[6dum]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6dum]] 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=6DUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DUM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6dum]] 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=6DUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DUM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A5Y:6-{[(3-fluorophenyl)methyl]sulfanyl}-2-(oxetan-3-yl)-5-phenyl-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one'>A5Y</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDH1A1, ALDC, ALDH1, PUMB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A5Y:6-{[(3-fluorophenyl)methyl]sulfanyl}-2-(oxetan-3-yl)-5-phenyl-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one'>A5Y</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dum OCA], [http://pdbe.org/6dum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dum RCSB], [http://www.ebi.ac.uk/pdbsum/6dum PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dum ProSAT]</span></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=6dum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dum OCA], [https://pdbe.org/6dum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dum RCSB], [https://www.ebi.ac.uk/pdbsum/6dum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dum ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[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).
-Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore the structural determinants of ALDH1A isoform selectivity in a series of small-molecule inhibitors in support of research into the role of ALDH1A in cancer stem cells. An SAR campaign guided by a cocrystal structure of the HTS hit CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily with excellent selectivity over the homologous ALDH2 isoform. We also discovered the first reported modestly selective single isoform 1A2 and 1A3 inhibitors. Two compounds, 13g and 13h, depleted the CD133(+) putative cancer stem cell pool, synergized with cisplatin, and achieved efficacious concentrations in vivo following IP administration. Compound 13h additionally synergized with cisplatin in a patient-derived ovarian cancer spheroid model.
-Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy.,Huddle BC, Grimley E, Buchman CD, Chtcherbinine M, Debnath B, Mehta P, Yang K, Morgan CA, Li S, Felton J, Sun D, Mehta G, Neamati N, Buckanovich RJ, Hurley TD, Larsen SD J Med Chem. 2018 Oct 11;61(19):8754-8773. doi: 10.1021/acs.jmedchem.8b00930. Epub, 2018 Sep 28. PMID:30221940<ref>PMID:30221940</ref>
+==See Also==
+*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6dum" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Buchman, C D]]
+[[Category: Buchman CD]]
-[[Category: Hurley, T D]]
+[[Category: Hurley TD]]
-[[Category: Oxidoreductase]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]