4ppr | pdb_00004ppr

Crystal structure of Mycobacterium tuberculosis D,D-peptidase Rv3330 in complex with meropenem

spinqualitylabelsall models 4ppr, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ppr is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: MER Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DACB1_MYCTU Probably cleaves the terminal D-Ala-D-Ala dipeptide of the peptidoglycan stem peptide (Probable). Shows weak D,D-carboxypeptidase activity in vitro (PubMed:22906310). Acts on the synthetic penta-peptide substrate Penta-DAP (L-Ala-gamma-D-Gln-DAP-D-Ala-D-Ala) (PubMed:22906310). The catalytic domain binds weakly to peptidoglycan in vitro (PubMed:25551456). 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. See Also Penicillin-binding protein 3D structures

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