1k57
OXA 10 class D beta-lactamase at pH 6.0
|
OverviewOverview
beta-Lactamases are the resistance enzymes for beta-lactam antibiotics, of, which four classes are known. beta-lactamases hydrolyze the beta-lactam, moieties of these antibiotics, rendering them inactive. It is shown herein, that the class D OXA-10 beta-lactamase depends critically on an unusual, carbamylated lysine as the basic residue for both the enzyme acylation and, deacylation steps of catalysis. The formation of carbamylated lysine is, reversible. Evidence is presented that this enzyme is dimeric and, carbamylated in living bacteria. High-resolution x-ray structures for the, native enzyme were determined at pH values of 6.0, 6.5, 7.5, and 8.5. Two, dimers are present per asymmetric unit. One monomer in each dimer was, carbamylated at pH 6.0, whereas all four monomers were fully carbamylated, at pH 8.5. At the intermediate pH values, one monomer of each dimer was, carbamylated, and the other showed a mixture of carbamylated and, non-carbamylated lysines. It would appear that, as the pH increased for, the sample, additional lysines were "titrated" by carbamylation. A handful, of carbamylated lysines are known from protein crystallographic data, all, of which have been attributed roles in structural stabilization (mostly as, metal ligands) of the proteins. This paper reports a previously, unrecognized role for a noncoordinated carbamylate lysine as a basic, residue involved in mechanistic reactions of an enzyme, which indicates, another means for expansion of the catalytic capabilities of the amino, acids in nature beyond the 20 common amino acids in development of, biological catalysts.
About this StructureAbout this Structure
1K57 is a Protein complex structure of sequences from Pseudomonas aeruginosa with SO4 as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Critical involvement of a carbamylated lysine in catalytic function of class D beta-lactamases., Golemi D, Maveyraud L, Vakulenko S, Samama JP, Mobashery S, Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14280-5. Epub 2001 Nov 27. PMID:11724923
Page seeded by OCA on Tue Nov 20 18:52:19 2007