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| | ==Crystal Structure of Antigen 85C and Glycerol== | | ==Crystal Structure of Antigen 85C and Glycerol== |
| - | <StructureSection load='3hrh' size='340' side='right' caption='[[3hrh]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3hrh' size='340' side='right'caption='[[3hrh]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hrh]] is a 2 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=3HRH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HRH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hrh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HRH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dqy|1dqy]], [[1dqz|1dqz]], [[1sfr|1sfr]], [[1f0n|1f0n]], [[1f0p|1f0p]], [[1va5|1va5]]</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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fbpC, fbpC2, mpt45, MT0137, MTCI5.03c, Rv0129c ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3hrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrh OCA], [https://pdbe.org/3hrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hrh RCSB], [https://www.ebi.ac.uk/pdbsum/3hrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrh ProSAT]</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=3hrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrh OCA], [http://pdbe.org/3hrh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hrh RCSB], [http://www.ebi.ac.uk/pdbsum/3hrh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hrh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A85C_MYCTU 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.<ref>PMID:1830294</ref> <ref>PMID:9162010</ref> | + | [https://www.uniprot.org/uniprot/A85C_MYCTU 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.<ref>PMID:1830294</ref> <ref>PMID:9162010</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3hrh" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3hrh" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antigen 85 3D structures|Antigen 85 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Boucau, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Ronning, D R]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Sanki, A K]] | + | [[Category: Boucau J]] |
| - | [[Category: Sucheck, S J]]
| + | [[Category: Ronning DR]] |
| - | [[Category: Umesiri, F E]] | + | [[Category: Sanki AK]] |
| - | [[Category: Acyltransferase]] | + | [[Category: Sucheck SJ]] |
| - | [[Category: Alpha/beta hydrolase]] | + | [[Category: Umesiri FE]] |
| - | [[Category: Hydrolase]] | + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Peptide-based 1,2-dicarbonyl compounds have emerged as potent inhibitors for serine proteases. Herein, we have designed and synthesized d-arabinose and d-trehalose-based esters, alpha-ketoesters and alpha-ketoamides, and evaluated their inhibitory activity against Mycobacterium tuberculosis (Mtb) antigen 85C (ag85C), an acyltransferase in the serine hydrolase superfamily. In addition the compounds were evaluated for the ability to inhibit the growth of Mycobacterium smegmatis ATCC 14 468, a non-pathogenic surrogate for Mtb. Among the synthetic analogs evaluated only the methyl ester derived from d-arabinose was found to inhibit the acyltransferase activity of ag85C (IC(50) = 25 mM). Based on this weak inhibitory activity it was not surprising that none of the compounds inhibits the growth of M. smegmatis. In spite of the weak inhibitory activity of , X-ray crystallography on crystals of ag85C soaked with suggested the formation of a covalent ester adduct between and the Ser124 side chain hydroxyl moiety found within the catalytic site of ag85C; however, some of the active site electron density appears to result from bound glycerol. The lack of activity associated with the alpha-ketoester and alpha-ketoamide derivatives of d-trehalose may be the result of intramolecular cyclization of the alpha-keto moiety with the nearby C-4/4' hydroxyls leading to the formation of stable bicyclo-ester and amide derivatives.
Design, synthesis and biological evaluation of sugar-derived esters, alpha-ketoesters and alpha-ketoamides as inhibitors for Mycobacterium tuberculosis antigen 85C.,Sanki AK, Boucau J, Umesiri FE, Ronning DR, Sucheck SJ Mol Biosyst. 2009 Sep;5(9):945-56. Epub 2009 Jun 19. PMID:19668859[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Sanki AK, Boucau J, Umesiri FE, Ronning DR, Sucheck SJ. Design, synthesis and biological evaluation of sugar-derived esters, alpha-ketoesters and alpha-ketoamides as inhibitors for Mycobacterium tuberculosis antigen 85C. Mol Biosyst. 2009 Sep;5(9):945-56. Epub 2009 Jun 19. PMID:19668859 doi:10.1039/b902284h
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