6as5: Difference between revisions
New page: '''Unreleased structure''' The entry 6as5 is ON HOLD Authors: Fedorov, A.A., Fedorov, E.V., Wang, H., Bonanno, J.B., Carvalho, L., Almo, S.C. Description: CRYSTAL STRUCTURE OF PROTEIN ... |
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==CRYSTAL STRUCTURE OF PROTEIN CitE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM, ACETOACETATE AND COENZYME A== | |||
<StructureSection load='6as5' size='340' side='right'caption='[[6as5]], [[Resolution|resolution]] 2.04Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6as5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AS5 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]] 2.035Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AAE:ACETOACETIC+ACID'>AAE</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6as5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6as5 OCA], [https://pdbe.org/6as5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6as5 RCSB], [https://www.ebi.ac.uk/pdbsum/6as5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6as5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CITEL_MYCTO CITEL_MYCTO] May play a role in fatty acid biosynthesis. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis. One-fourth of the global population is estimated to be infected with Mtb, accounting for approximately 1.3 million deaths in 2017. As part of the immune response to Mtb infection, macrophages produce metabolites with the purpose of inhibiting or killing the bacterial cell. Itaconate is an abundant host metabolite thought to be both an antimicrobial agent and a modulator of the host inflammatory response. However, the exact mode of action of itaconate remains unclear. Here, we show that Mtb has an itaconate dissimilation pathway and that the last enzyme in this pathway, Rv2498c, also participates in l-leucine catabolism. Our results from phylogenetic analysis, in vitro enzymatic assays, X-ray crystallography, and in vivo Mtb experiments, identified Mtb Rv2498c as a bifunctional beta-hydroxyacyl-CoA lyase and that deletion of the rv2498c gene from the Mtb genome resulted in attenuation in a mouse infection model. Altogether, this report describes an itaconate resistance mechanism in Mtb and an l-leucine catabolic pathway that proceeds via an unprecedented (R)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) stereospecific route in nature. | |||
An essential bifunctional enzyme in Mycobacterium tuberculosis for itaconate dissimilation and leucine catabolism.,Wang H, Fedorov AA, Fedorov EV, Hunt DM, Rodgers A, Douglas HL, Garza-Garcia A, Bonanno JB, Almo SC, de Carvalho LPS Proc Natl Acad Sci U S A. 2019 Jul 18. pii: 1906606116. doi:, 10.1073/pnas.1906606116. PMID:31320588<ref>PMID:31320588</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6as5" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Bonanno | <references/> | ||
[[Category: Carvalho | __TOC__ | ||
[[Category: Fedorov | </StructureSection> | ||
[[Category: Wang | [[Category: Large Structures]] | ||
[[Category: Mycobacterium tuberculosis H37Rv]] | |||
[[Category: Almo SC]] | |||
[[Category: Bonanno JB]] | |||
[[Category: Carvalho L]] | |||
[[Category: Fedorov AA]] | |||
[[Category: Fedorov EV]] | |||
[[Category: Wang H]] | |||