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4mqm

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Revision as of 13:03, 5 August 2016

Crystal structure of Antigen 85C in presence of Ebselen

Structural highlights

4mqm is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4mql
Gene:	fbpC, mpt45, Rv0129c, MT0137, MTCI5.03c ("Bacillus tuberculosis" (Zopf 1883) Klein 1884)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[A85C_MYCTU] The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria to fibronectin, a large adhesive glycoprotein, which facilitates the attachment of M.tuberculosis to murine alveolar macrophages (AMs). They also help to maintain the integrity of the cell wall by catalyzing the transfer of mycolic acids to cell wall arabinogalactan and through the synthesis of alpha,alpha-trehalose dimycolate (TDM, cord factor). They catalyze the transfer of a mycoloyl residue from one molecule of alpha,alpha-trehalose monomycolate (TMM) to another TMM, leading to the formation of TDM.^[1] ^[2]

Publication Abstract from PubMed

The increasing prevalence of drug-resistant tuberculosis highlights the need for identifying new antitubercular drugs that can treat these infections. The antigen 85 (Ag85) complex has emerged as an intriguing mycobacterial drug target due to its central role in synthesizing major components of the inner and outer leaflets of the mycobacterial outer membrane. Here we identify ebselen (EBS) as a potent inhibitor of the Mycobacterium tuberculosis Ag85 complex. Mass spectrometry data show that EBS binds covalently to a cysteine residue (C209) located near the Ag85C active site. The crystal structure of Ag85C in the presence of EBS shows that C209 modification restructures the active site, thereby disrupting the hydrogen-bonded network within the active site that is essential for enzymatic activity. C209 mutations display marked decreases in enzymatic activity. These data suggest that compounds using this mechanism of action will strongly inhibit the Ag85 complex and minimize the selection of drug resistance.

Mechanism of inhibition of Mycobacterium tuberculosis antigen 85 by ebselen.,Favrot L, Grzegorzewicz AE, Lajiness DH, Marvin RK, Boucau J, Isailovic D, Jackson M, Ronning DR Nat Commun. 2013;4:2748. doi: 10.1038/ncomms3748. PMID:24193546^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Abou-Zeid C, Garbe T, Lathigra R, Wiker HG, Harboe M, Rook GA, Young DB. Genetic and immunological analysis of Mycobacterium tuberculosis fibronectin-binding proteins. Infect Immun. 1991 Aug;59(8):2712-8. PMID:1830294
↑ Belisle JT, Vissa VD, Sievert T, Takayama K, Brennan PJ, Besra GS. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science. 1997 May 30;276(5317):1420-2. PMID:9162010
↑ Favrot L, Grzegorzewicz AE, Lajiness DH, Marvin RK, Boucau J, Isailovic D, Jackson M, Ronning DR. Mechanism of inhibition of Mycobacterium tuberculosis antigen 85 by ebselen. Nat Commun. 2013;4:2748. doi: 10.1038/ncomms3748. PMID:24193546 doi:http://dx.doi.org/10.1038/ncomms3748

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4mqm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Antigen 85C in presence of Ebselen==
 <StructureSection load='4mqm' size='340' side='right' caption='[[4mqm]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mql|4mql]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fbpC, mpt45, Rv0129c, MT0137, MTCI5.03c ([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=4mqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mqm RCSB], [http://www.ebi.ac.uk/pdbsum/4mqm PDBsum]</span></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=4mqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mqm OCA], [http://pdbe.org/4mqm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mqm RCSB], [http://www.ebi.ac.uk/pdbsum/4mqm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mqm ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4mqm" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antigen 85|Antigen 85]]
 == References ==
 <references/>

4mqm

From Proteopedia

Revision as of 13:03, 5 August 2016

Crystal structure of Antigen 85C in presence of Ebselen

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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