6con
From Proteopedia
(Difference between revisions)
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<StructureSection load='6con' size='340' side='right' caption='[[6con]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='6con' size='340' side='right' caption='[[6con]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6con]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CON OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CON FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6con]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CON OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CON FirstGlance]. <br> |
| - | </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=6con FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6con OCA], [http://pdbe.org/6con PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6con RCSB], [http://www.ebi.ac.uk/pdbsum/6con PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6con ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gctA, CRX58_09925, ERS007663_04080, ERS007665_02371, ERS023446_02783, ERS027646_00148, ERS027654_03521, ERS027656_00696, ERS124361_01188, SAMEA2682864_02618, SAMEA2683035_00650 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), catJ, CRX58_09930, ERS007657_01926, ERS007661_02237, ERS007665_02370, ERS007670_03185, ERS007672_03945, ERS007679_04090, ERS007681_03977, ERS007688_03438, ERS007703_04697, ERS007722_01813, ERS007741_03174, ERS023446_02782, ERS024213_01521, ERS024276_02483, ERS027644_04603, ERS027646_00147, ERS027656_00695, ERS027659_03102, ERS027661_03605, ERS027666_03707, ERS124361_01187, SAMEA2682864_02619, SAMEA2683035_00651 ([http://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='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=6con FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6con OCA], [http://pdbe.org/6con PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6con RCSB], [http://www.ebi.ac.uk/pdbsum/6con PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6con ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mycobacterium tuberculosis (Mtb) grows on host-derived cholesterol during infection. IpdAB, found in all steroid-degrading bacteria and a determinant of pathogenicity, has been implicated in the hydrolysis of the last steroid ring. Phylogenetic analyses revealed that IpdAB orthologs form a clade of CoA transferases (CoTs). In a coupled assay with a thiolase, IpdAB transformed the cholesterol catabolite (R)-2-(2-carboxyethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA (COCHEA-CoA) and CoASH to 4-methyl-5-oxo-octanedioyl-CoA (MOODA-CoA) and acetyl-CoA with high specificity (kcat/Km = 5.8 +/- 0.8 x 10(4) M(-1)s(-1)). The structure of MOODA-CoA was consistent with IpdAB hydrolyzing COCHEA-CoA to a beta-keto-thioester, a thiolase substrate. Contrary to characterized CoTs, IpdAB exhibited no activity toward small CoA thioesters. Further, IpdAB lacks the catalytic glutamate residue that is conserved in the beta-subunit of characterized CoTs and a glutamyl-CoA intermediate was not trapped during turnover. By contrast, Glu105(A), conserved in the alpha-subunit of IpdAB, was essential for catalysis. A crystal structure of the IpdAB.COCHEA-CoA complex, solved to 1.4 A, revealed that Glu105(A) is positioned to act as a catalytic base. Upon titration with COCHEA-CoA, the E105A(A) variant accumulated a yellow-colored species (lambdamax = 310 nm; Kd = 0.4 +/- 0.2 muM) typical of beta-keto enolates. In the presence of D2O, IpdAB catalyzed the deuteration of COCHEA-CoA adjacent to the hydroxylation site at rates consistent with kcat Based on these data and additional IpdAB variants, we propose a retro-Claisen condensation-like mechanism for the IpdAB-mediated hydrolysis of COCHEA-CoA. This study expands the range of known reactions catalyzed by the CoT superfamily and provides mechanistic insight into an important determinant of Mtb pathogenesis. | ||
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| + | IpdAB, a virulence factor in Mycobacterium tuberculosis, is a cholesterol ring-cleaving hydrolase.,Crowe AM, Workman SD, Watanabe N, Worrall LJ, Strynadka NCJ, Eltis LD Proc Natl Acad Sci U S A. 2018 Mar 26. pii: 1717015115. doi:, 10.1073/pnas.1717015115. PMID:29581275<ref>PMID:29581275</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6con" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 14:22, 11 April 2018
Crystal structure of Mycobacterium tuberculosis IpdAB
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