2ov5
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(New page: 200px<br /><applet load="2ov5" size="350" color="white" frame="true" align="right" spinBox="true" caption="2ov5, resolution 1.850Å" /> '''Crystal structure o...)
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Revision as of 13:04, 23 January 2008
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Crystal structure of the KPC-2 carbapenemase
Overview
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.
About this Structure
2OV5 is a Single protein structure of sequence from Klebsiella pneumoniae with as ligand. Active as Hydrolase, with EC number 3.5.2.6. Full crystallographic information is available from OCA.
Reference
Crystal Structure of KPC-2: Insights into Carbapenemase Activity in Class A beta-Lactamases(,)., Ke W, Bethel CR, Thomson JM, Bonomo RA, Akker FV, Biochemistry. 2007 Apr 19;. PMID:17441734
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