4p0m

Crystal structure of an evolved putative penicillin-binding protein homolog, Rv2911, from Mycobacterium tuberculosis

spinqualitylabelsall models 4p0m, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p0m is a 1 chain structure with sequence from Mycobacterium tuberculosis. This structure supersedes the now removed PDB entry 2bcf. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: MSE, SEB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q7D6F2_MYCTO Publication Abstract from PubMed Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows that Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis. Subfamily-Specific Adaptations in the Structures of Two Penicillin-Binding Proteins from Mycobacterium tuberculosis.,Prigozhin DM, Krieger IV, Huizar JP, Mavrici D, Waldo GS, Hung LW, Sacchettini JC, Terwilliger TC, Alber T PLoS One. 2014 Dec 31;9(12):e116249. doi: 10.1371/journal.pone.0116249., eCollection 2014. PMID:25551456 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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