4x4l: Difference between revisions

Revision as of 21:11, 12 April 2023

Structure of human ALDH1A1 with inhibitor CM037

Structural highlights

4x4l is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	3XG, CL, NA, NAI, YB
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AL1A1_HUMAN Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity).

Publication Abstract from PubMed

Aldehyde dehydrogenases (ALDH) catalyze the irreversible oxidation of aldehydes to their corresponding carboxylic acid. Alterations in ALDH1A1 activity are associated with such diverse diseases as cancer, Parkinson's disease, obesity, and cataracts. Inhibitors of ALDH1A1 could aid in illuminating the role of this enzyme in disease processes. However, there are no commercially available selective inhibitors for ALDH1A1. Here we characterize two distinct chemical classes of inhibitors that are selective for human ALDH1A1 compared to eight other ALDH isoenzymes. The prototypical members of each structural class, CM026 and CM037, exhibit submicromolar inhibition constants but have different mechanisms of inhibition. The crystal structures of these compounds bound to ALDH1A1 demonstrate that they bind within the aldehyde binding pocket of ALDH1A1 and exploit the presence of a unique glycine residue to achieve their selectivity. These two novel and selective ALDH1A1 inhibitors may serve as chemical tools to better understand the contributions of ALDH1A1 to normal biology and to disease states.

Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors.,Morgan CA, Hurley TD J Med Chem. 2015 Feb 10. PMID:25634381^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Morgan CA, Hurley TD. Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors. J Med Chem. 2015 Feb 10. PMID:25634381 doi:https://dx.doi.org/10.1021/jm501900s

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OCA

[1] Morgan CA, Hurley TD. Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors. J Med Chem. 2015 Feb 10. PMID:25634381 doi:https://dx.doi.org/10.1021/jm501900s

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='4x4l' size='340' side='right'caption='[[4x4l]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x4l]] 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=4X4L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X4L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x4l]] 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=4X4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X4L FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3XG:ETHYL+({4-OXO-3-[3-(PYRROLIDIN-1-YL)PROPYL]-3,4-DIHYDRO[1]BENZOTHIENO[3,2-D]PYRIMIDIN-2-YL}SULFANYL)ACETATE'>3XG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3XG:ETHYL+({4-OXO-3-[3-(PYRROLIDIN-1-YL)PROPYL]-3,4-DIHYDRO[1]BENZOTHIENO[3,2-D]PYRIMIDIN-2-YL}SULFANYL)ACETATE'>3XG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wp7|4wp7]]</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=4x4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x4l OCA], [https://pdbe.org/4x4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x4l RCSB], [https://www.ebi.ac.uk/pdbsum/4x4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x4l ProSAT]</span></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='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=4x4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x4l OCA], [http://pdbe.org/4x4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x4l RCSB], [http://www.ebi.ac.uk/pdbsum/4x4l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x4l ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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).
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Retinal dehydrogenase]]
+[[Category: Hurley TD]]
-[[Category: Hurley, T D]]
+[[Category: Morgan CA]]
-[[Category: Morgan, C A]]
-[[Category: Oxidoreductase enzyme inhibitor]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

4x4l: Difference between revisions

Revision as of 21:11, 12 April 2023

Structure of human ALDH1A1 with inhibitor CM037

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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