1sfr | pdb_00001sfr
Crystal Structure of the Mycobacterium tuberculosis Antigen 85A Protein
Structural highlights
FunctionA85A_MYCTU The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible for the high affinity of mycobacteria for 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. FbpA mediates triacylglycerol (TAG) formation with long-chain acyl-CoA as the acyl donor and 1,2-dipalmitoyl-sn-glycerol (1,2-dipalmitin) as the acyl acceptor. It has a preference for C26:0-CoA over C18:1-CoA.[1] [2] [3] [4] 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 PubMedThe maintenance of the highly hydrophobic cell wall is central to the survival of Mycobacterium tuberculosis within its host environment. The antigen 85 proteins (85A, 85B, and 85C) of M. tuberculosis help maintain the integrity of the cell wall 1) by catalyzing the transfer of mycolic acids to the cell wall arabinogalactan and 2) through the synthesis of trehalose dimycolate (cord factor). Additionally, these secreted proteins allow for rapid invasion of alveolar macrophages via direct interactions between the host immune system and the invading bacillus. Here we describe two crystal structures: the structure of antigen 85C co-crystallized with octylthioglucoside as substrate, resolved to 2.0 A, and the crystal structure of antigen 85A, which was solved at a resolution of 2.7 A. The structure of 85C with the substrate analog identifies residues directly involved in substrate binding. Elucidation of the antigen 85A structure, the last of the three antigen 85 homologs to be solved, shows that the active sites of the three antigen 85 proteins are virtually identical, indicating that these share the same substrate. However, in contrast to the high level of conservation within the substrate-binding site and the active site, surface residues disparate from the active site are quite variable, indicating that three antigen 85 enzymes are needed to evade the host immune system. Mycobacterium tuberculosis antigen 85A and 85C structures confirm binding orientation and conserved substrate specificity.,Ronning DR, Vissa V, Besra GS, Belisle JT, Sacchettini JC J Biol Chem. 2004 Aug 27;279(35):36771-7. Epub 2004 Jun 10. PMID:15192106[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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