3vos: Difference between revisions
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The | ==Crystal structure of Aspartate semialdehyde dehydrogenase Complexed With glycerol and sulfate From Mycobacterium tuberculosis H37Rv== | ||
<StructureSection load='3vos' size='340' side='right'caption='[[3vos]], [[Resolution|resolution]] 2.18Å' scene=''> | |||
== Structural highlights == | |||
<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='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='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='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> | |||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:22683789</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3vos" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]] | |||
*[[Aspartate-semialdehyde dehydrogenase 3D structures|Aspartate-semialdehyde dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | |||
[[Category: Karthikeyan S]] | |||
[[Category: Tewari R]] | |||
[[Category: Vyas R]] | |||
[[Category: Weiss MS]] | |||
Latest revision as of 15:30, 8 November 2023
Crystal structure of Aspartate semialdehyde dehydrogenase Complexed With glycerol and sulfate From Mycobacterium tuberculosis H37RvCrystal structure of Aspartate semialdehyde dehydrogenase Complexed With glycerol and sulfate From Mycobacterium tuberculosis H37Rv
Structural highlights
FunctionDHAS_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 PubMedAspartate-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 AlsoReferences
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