1sml
From Proteopedia
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METALLO BETA LACTAMASE L1 FROM STENOTROPHOMONAS MALTOPHILIA
Overview
The structure of the L1 metallo-beta-lactamase from the opportunistic, pathogen Stenotrophomonas maltophilia has been determined at 1.7 A, resolution by the multiwavelength anomalous dispersion (MAD) approach, exploiting both the intrinsic binuclear zinc centre and incorporated, selenomethionine residues. L1 is unique amongst all known beta-lactamases, in that it exists as a tetramer. The protein exhibits the, alphabeta/betaalpha fold found only in the metallo-beta-lactamases and, displays several unique features not previously observed in these enzymes., These include a disulphide bridge and two substantially elongated loops, connected to the active site of the enzyme. Two closely spaced zinc ions, are bound at the active site with tetrahedral (Zn1) and trigonal, bipyramidal (Zn2) co-ordination, respectively; these are bridged by a, water molecule which we propose acts as the nucleophile in the hydrolytic, reaction. Ligation of the second zinc ion involves both residues and, geometry which have not been previously observed in the, metallo-beta-lactamases. Simulated binding of the substrates ampicillin, ceftazidime and imipenem suggests that the substrate is able to bind to, the enzyme in a variety of different conformations whose common features, are direct interactions of the beta-lactam carbonyl oxygen and nitrogen, with the zinc ions and of the beta-lactam carboxylate with Ser187. We, describe a catalytic mechanism whose principal features are a nucleophilic, attack of the bridging water on the beta-lactam carbonyl carbon, electrostatic stabilisation of a negatively charged tetrahedral transition, state and protonation of the beta-lactam nitrogen by a second water, molecule co-ordinated by Zn2. Further, we propose that direct, metal:substrate interactions provide a substantial contribution to, substrate binding and that this may explain the lack of specificity which, is a feature of this class of enzyme.
About this Structure
1SML is a Single protein structure of sequence from Stenotrophomonas maltophilia with ZN as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
The crystal structure of the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia at 1.7 A resolution., Ullah JH, Walsh TR, Taylor IA, Emery DC, Verma CS, Gamblin SJ, Spencer J, J Mol Biol. 1998 Nov 20;284(1):125-36. PMID:9811546
Page seeded by OCA on Wed Nov 21 02:29:27 2007
