6c89

NDM-1 Beta-Lactamase Exhibits Differential Active Site Sequence Requirements for the Hydrolysis of Penicillin versus Carbapenem Antibiotics

spinqualitylabelsall models 6c89, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6c89 is a 4 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7500615Å Ligands: CL, EDO, GOL, NA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E5KIY2_ECOLX Publication Abstract from PubMed New Delhi metallo-beta-lactamase-1 exhibits a broad substrate profile for hydrolysis of the penicillin, cephalosporin and 'last resort' carbapenems, and thus confers bacterial resistance to nearly all beta-lactam antibiotics. Here we address whether the high catalytic efficiency for hydrolysis of these diverse substrates is reflected by similar sequence and structural requirements for catalysis, i.e., whether the same catalytic machinery is used to achieve hydrolysis of each class. Deep sequencing of randomized single codon mutation libraries that were selected for resistance to representative antibiotics reveal stringent sequence requirements for carbapenem versus penicillin or cephalosporin hydrolysis. Further, the residue positions required for hydrolysis of penicillins and cephalosporins are a subset of those required for carbapenem hydrolysis. Thus, while a common core of residues is used for catalysis of all substrates, carbapenem hydrolysis requires an additional set of residues to achieve catalytic efficiency comparable to that for penicillins and cephalosporins. Differential active site requirements for NDM-1 beta-lactamase hydrolysis of carbapenem versus penicillin and cephalosporin antibiotics.,Sun Z, Hu L, Sankaran B, Prasad BVV, Palzkill T Nat Commun. 2018 Oct 30;9(1):4524. doi: 10.1038/s41467-018-06839-1. PMID:30375382 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA