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| | <StructureSection load='3q0e' size='340' side='right'caption='[[3q0e]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='3q0e' size='340' side='right'caption='[[3q0e]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3q0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q0E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3q0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q0E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3q11|3q11]], [[3pzb|3pzb]], [[3pwk|3pwk]], [[3pyl|3pyl]], [[3pws|3pws]], [[3pzr|3pzr]], [[3pyx|3pyx]], [[3q1l|3q1l]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VC_2036 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 "Bacillo virgola del Koch" Trevisan 1884])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aspartate-semialdehyde_dehydrogenase Aspartate-semialdehyde dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.11 1.2.1.11] </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=3q0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q0e OCA], [https://pdbe.org/3q0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q0e RCSB], [https://www.ebi.ac.uk/pdbsum/3q0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q0e 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=3q0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q0e OCA], [https://pdbe.org/3q0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q0e RCSB], [https://www.ebi.ac.uk/pdbsum/3q0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q0e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DHAS1_VIBCH DHAS1_VIBCH]] Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate.<ref>PMID:12071715</ref>
| + | [https://www.uniprot.org/uniprot/DHAS1_VIBCH DHAS1_VIBCH] Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate.<ref>PMID:12071715</ref> |
| | <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: Bacillo virgola del koch trevisan 1884]] | |
| - | [[Category: Aspartate-semialdehyde dehydrogenase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liu, X]] | + | [[Category: Vibrio cholerae]] |
| - | [[Category: Pavlovsky, A G]] | + | [[Category: Liu X]] |
| - | [[Category: Viola, R E]] | + | [[Category: Pavlovsky AG]] |
| - | [[Category: Nadp]] | + | [[Category: Viola RE]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxydoreductase]]
| + | |
| Structural highlights
Function
DHAS1_VIBCH Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate.[1]
Publication Abstract from PubMed
The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, l-aspartate-beta-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the l-aspartate-beta-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against l-aspartate-beta-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors.
Structural Characterization of Inhibitors with Selectivity against Members of a Homologous Enzyme Family.,Pavlovsky AG, Liu X, Faehnle CR, Potente N, Viola RE Chem Biol Drug Des. 2012 Jan;79(1):128-36. doi:, 10.1111/j.1747-0285.2011.01267.x. Epub 2011 Nov 28. PMID:22039970[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moore RA, Bocik WE, Viola RE. Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms. Protein Expr Purif. 2002 Jun;25(1):189-94. PMID:12071715 doi:http://dx.doi.org/10.1006/prep.2002.1626
- ↑ Pavlovsky AG, Liu X, Faehnle CR, Potente N, Viola RE. Structural Characterization of Inhibitors with Selectivity against Members of a Homologous Enzyme Family. Chem Biol Drug Des. 2012 Jan;79(1):128-36. doi:, 10.1111/j.1747-0285.2011.01267.x. Epub 2011 Nov 28. PMID:22039970 doi:10.1111/j.1747-0285.2011.01267.x
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