ISSN:
0887-3585
Keywords:
β-lactamase
;
penicillinase
;
penicillin-binding protein
;
penicillin antibiotics
;
X-ray diffraction
;
protein structure prediction
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
Two crystal (A and B) of the 29,500 Da Class A β-lactamase (penicillinase) from Bacillus licheniformis 749/C have been examined crystallographically. The structure of B-form crystals has been solved to 2 Å resolution, the starting model for which was a 3.5 Å structure obtained from A-form crystals. The β-lactamase has an α + β structure with 11 helices and 5 β-strands seen also in a peinicilin target DD-peptidase of Streptomyces R61.1 Atomic parameters of the two molecules in the asymmetric unit were refined by simulated annealing at 2.0 Å resolution. The R factor is 0.208 for the 27,330 data greater than 3 (F), with water molecules excluded from the model. The catalytic Ser-70 is at the N-terminus of a helix and is within hydrogen bonding distance of conversed Lys-73. Also interacting with the Lys-73 are Asn-132 and the conserved Glu-166, which is on a potentially flexible helix-containing loop. The structure suggests the binding of β-lactam substrates is facilitated by interactions with Lys-234, Tyhr-235, and Ala-237 in a conserved β-strand peptide, which is antiparallel to the β-lactam's acylamido linkage; an exposed cavity near Asn-170 exits for acylamido Substituent. The reactive double bond of clavulanate-type inhibitors may interact with Arg-244 on the fourth β-strand. A very similar binding site architecture is seen in the DD-peptidase.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/prot.340070205
Permalink
