2ov5

Crystal structure of the KPC-2 carbapenemaseCrystal structure of the KPC-2 carbapenemase

Structural highlights 2ov5 is a 3 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLKPC_KLEPN Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. 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 PubMed Beta-lactamases inactivate beta-lactam antibiotics and are a major cause of antibiotic resistance. The recent outbreaks of Klebsiella pneumoniae carbapenem resistant (KPC) infections mediated by KPC type beta-lactamases are creating a serious threat to our "last resort" antibiotics, the carbapenems. KPC beta-lactamases are serine carbapenemases and are a subclass of class A beta-lactamases that have evolved to efficiently hydrolyze carbapenems and cephamycins which contain substitutions at the alpha-position proximal to the carbonyl group that normally render these beta-lactams resistant to hydrolysis. To investigate the molecular basis of this carbapenemase activity, we have determined the structure of KPC-2 at 1.85 A resolution. The active site of KPC-2 reveals the presence of a bicine buffer molecule which interacts via its carboxyl group with conserved active site residues S130, K234, T235, and T237; these likely resemble the interactions the beta-lactam carboxyl moiety makes in the Michaelis-Menten complex. Comparison of the KPC-2 structure with non-carbapenemases and previously determined NMC-A and SME-1 carbapenemase structures shows several active site alterations that are unique among carbapenemases. An outward shift of the catalytic S70 residue renders the active sites of the carbapenemases more shallow, likely allowing easier access of the bulkier substrates. Further space for the alpha-substituents is potentially provided by shifts in N132 and N170 in addition to concerted movements in the postulated carboxyl binding pocket that might allow the substrates to bind at a slightly different angle to accommodate these alpha-substituents. The structure of KPC-2 provides key insights into the carbapenemase activity of emerging class A beta-lactamases. Crystal structure of KPC-2: insights into carbapenemase activity in class A beta-lactamases.,Ke W, Bethel CR, Thomson JM, Bonomo RA, van den Akker F Biochemistry. 2007 May 15;46(19):5732-40. Epub 2007 Apr 19. PMID:17441734 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 2ov5, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image