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| | <StructureSection load='3vos' size='340' side='right'caption='[[3vos]], [[Resolution|resolution]] 2.18Å' scene=''> | | <StructureSection load='3vos' size='340' side='right'caption='[[3vos]], [[Resolution|resolution]] 2.18Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vos]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3llg 3llg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3kub 3kub]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VOS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vos]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3llg 3llg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3kub 3kub]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VOS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.18Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3tz6|3tz6]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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">asd, MT3811, MTV025.056c, Rv3708c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 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=3vos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vos OCA], [https://pdbe.org/3vos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vos RCSB], [https://www.ebi.ac.uk/pdbsum/3vos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vos 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=3vos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vos OCA], [https://pdbe.org/3vos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vos RCSB], [https://www.ebi.ac.uk/pdbsum/3vos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vos ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DHAS_MYCTU DHAS_MYCTU]] Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate.<ref>PMID:15752328</ref>
| + | [https://www.uniprot.org/uniprot/DHAS_MYCTU DHAS_MYCTU] Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate.<ref>PMID:15752328</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: Aspartate-semialdehyde dehydrogenase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Karthikeyan, S]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Tewari, R]] | + | [[Category: Karthikeyan S]] |
| - | [[Category: Vyas, R]] | + | [[Category: Tewari R]] |
| - | [[Category: Weiss, M S]] | + | [[Category: Vyas R]] |
| - | [[Category: Amino-acid biosynthesis]] | + | [[Category: Weiss MS]] |
| - | [[Category: Dehydrogenase]]
| + | |
| - | [[Category: Lysine biosynthesis]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DHAS_MYCTU 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
Aspartate-semialdehyde dehydrogenase (Asd; ASADH; EC 1.2.1.11) is the enzyme that lies at the first branch point in the biosynthetic pathway of important amino acids including lysine and methionine and the cell-wall component diaminopimelate (DAP). The enzymatic reaction of ASADH is the reductive dephosphorylation of aspartyl-beta-phosphate (ABP) to aspartate beta-semialdehyde (ASA). Since the aspartate pathway is absolutely essential for the survival of many microbes and is absent in humans, the enzymes involved in this pathway can be considered to be potential antibacterial drug targets. In this work, the structure of ASADH from Mycobacterium tuberculosis H37Rv (Mtb-ASADH) has been determined in complex with glycerol and sulfate at 2.18 A resolution and in complex with S-methyl-L-cysteine sulfoxide (SMCS) and sulfate at 1.95 A resolution. The overall structure of Mtb-ASADH is similar to those of its orthologues. However, in the Mtb-ASADH-glycerol complex structure the glycerol molecule is noncovalently bound to the active-site residue Cys130, while in the Mtb-ASADH-SMCS complex structure the SMCS (Cys) is covalently linked to Cys130. The Mtb-ASADH-SMCS complex structurally mimics one of the intermediate steps in the proposed mechanism of ASADH enzyme catalysis. Comparison of the two complex structures revealed that the amino acids Glu224 and Arg249 undergo conformational changes upon binding of glycerol. Moreover, the structures reported here may help in the development of species-specific antibacterial drug molecules against human pathogens.
Structures of ternary complexes of aspartate-semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis H37Rv.,Vyas R, Tewari R, Weiss MS, Karthikeyan S Acta Crystallogr D Biol Crystallogr. 2012 Jun;68(Pt 6):671-9. doi:, 10.1107/S0907444912007330. Epub 2012 May 17. PMID:22683789[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shafiani S, Sharma P, Vohra RM, Tewari R. Cloning and characterization of aspartate-beta-semialdehyde dehydrogenase from Mycobacterium tuberculosis H37 Rv. J Appl Microbiol. 2005;98(4):832-8. PMID:15752328 doi:10.1111/j.1365-2672.2004.02505.x
- ↑ Vyas R, Tewari R, Weiss MS, Karthikeyan S. Structures of ternary complexes of aspartate-semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis H37Rv. Acta Crystallogr D Biol Crystallogr. 2012 Jun;68(Pt 6):671-9. doi:, 10.1107/S0907444912007330. Epub 2012 May 17. PMID:22683789 doi:10.1107/S0907444912007330
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