1K54: Oxa-10 Class D Beta-lactamase Partially Acylated With Reacted 6beta- (1-hydroxy-1-methylethyl) Penicillanic Acid

Citation:
Abstract
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.
PDB ID: 1K54Download
MMDB ID: 17581
PDB Deposition Date: 2001/10/10
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 1K54: dimeric; determined by author and by software (PQS)
Molecular Components in 1K54
Label Count Molecule
Proteins (2 molecules)
1
Beta Lactamase Oxa-10
Molecule annotation
1
Beta Lactamase Oxa-10
Molecule annotation
Chemicals (12 molecules)
1
9
2
1
3
2
* Click molecule labels to explore molecular sequence information.

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