5oiz | pdb_00005oiz

Penicillin-Binding Protein 2X (PBP2X) from Streptococcus pneumoniae in complex with oxacillin

spinqualitylabelsall models 5oiz, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5oiz is a 1 chain structure with sequence from Strr6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1S6 Gene: pbpX, spr0304 (STRR6) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PBPX_STRR6] Penicillin-binding proteins (PBPs) function in the late steps of murein biosynthesis. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins. Publication Abstract from PubMed Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by beta-lactam antibiotics. We report herein our structural insights into catalysis by the essential PBP2x of Streptococcus pneumoniae by disclosing a total of four X-ray structures, two computational models based on the crystal structures, and molecular-dynamics simulations. The X-ray structures are for the apo PBP2x, the enzyme modified covalently in the active site by oxacillin (a penicillin antibiotic), the enzyme modified by oxacillin in the presence of a synthetic tetrasaccharide surrogate for the cell-wall peptidoglycan, and a noncovalent complex of cefepime (a cephalosporin antibiotic) bound to the active site. A prerequisite for catalysis by transpeptidases, including PBP2x, is the molecular recognition of nascent peptidoglycan strands, which harbor pentapeptide stems. We disclose that the recognition of nascent peptidoglycan by PBP2x takes place by complexation of one pentapeptide stem at an allosteric site located in the PASTA domains of this enzyme. This binding predisposes the third pentapeptide stem in the same nascent peptidoglycan strand to penetration into the active site for the turnover events. The complexation of the two pentapeptide stems in the same peptidoglycan strand is a recognition motif for the nascent peptidoglycan, critical for the cell-wall cross-linking reaction. Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae.,Bernardo-Garcia N, Mahasenan KV, Batuecas MT, Lee M, Hesek D, Petrackova D, Doubravova L, Branny P, Mobashery S, Hermoso JA ACS Chem Biol. 2018 Mar 16;13(3):694-702. doi: 10.1021/acschembio.7b00817. Epub, 2018 Jan 30. PMID:29357220 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA