Penicillin and cephalosporin biosynthesis
Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis.
Evolution of an enzyme activity: crystallographic structure at 2-A resolution of cephalosporinase from the ampC gene of Enterobacter cloacae P99 and comparison with a class A penicillinase.
Role of residue Lys315 in the mechanism of action of the Enterobacter cloacae 908R beta-lactamase.
Crystallographic structure of a phosphonate derivative of the Enterobacter cloacae P99 cephalosporinase: mechanistic interpretation of a beta-lactamase transition-state analog.
The role of tyrosine 150 in catalysis of beta-lactam hydrolysis by AmpC beta-lactamase from Escherichia coli investigated by site-directed mutagenesis.
X-ray crystallography (2.0-2.3 Angstroms)
Three-dimensional structure of AmpC beta-lactamase from Escherichia coli bound to a transition-state analogue: possible implications for the oxyanion hypothesis and for inhibitor design.
Beta-secondary and solvent deuterium kinetic isotope effects on catalysis by the Streptomyces R61 DD-peptidase: comparisons with a structurally similar class C beta-lactamase.
Structure-function studies of Ser-289 in the class C beta-lactamase from Enterobacter cloacae P99.
Structure of the extended-spectrum class C beta-lactamase of Enterobacter cloacae GC1, a natural mutant with a tandem tripeptide insertion.
The complexed structure and antimicrobial activity of a non-beta-lactam inhibitor of AmpC beta-lactamase.
Crystal structures of substrate and inhibitor complexes with ampc -lactamase: possible implications for substrate-assisted catalysis.
Expression, purification, crystallization and preliminary X-ray analysis of the native class C beta-lactamase from Enterobacter cloacae 908R and two mutants.
X-ray crystallography (1.75/1.90 Angstroms)
Energetic, structural, and antimicrobial analyses of beta-lactam side chain recognition by beta-lactamases.
Mechanism of reaction of acyl phosph(on)ates with the beta-lactamase of Enterobacter cloacae P99.
The relative catalytic efficiency of beta-lactamase catalyzed acyl and phosphyl transfer.
Inhibition of class C beta-lactamases: structure of a reaction intermediate with a cephem sulfone.
Inhibition of AmpC beta-lactamase through a destabilizing interaction in the active site.
Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: implications for resistance mutations and inhibitor design.
Binding properties of a peptide derived from beta-lactamase inhibitory protein.
Mechanism of inhibition of the beta-lactamase of Enterobacter cloacae P99 by 1:1 complexes of vanadate with hydroxamic acids.
Structural milestones in the reaction pathway of an amide hydrolase: substrate, acyl, and product complexes of cephalothin with AmpC beta-lactamase.
Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase.
Structural basis for imipenem inhibition of class C beta-lactamases.
Chemical complementation: a reaction-independent genetic assay for enzyme catalysis.
pKa measurements from nuclear magnetic resonance of tyrosine-150 in class C beta-lactamase.
Role of beta-lactam carboxyl group on binding of penicillins and cephalosporins to class C beta-lactamases.
Structural aspects for evolution of beta-lactamases from penicillin-binding proteins.
Crystal structure of Enterobacter cloacae 908R class C beta-lactamase bound to iodo-acetamido-phenyl boronic acid, a transition-state analogue.
This enzyme belongs to the class-C beta-lactamase family. Ser64 acts as a nucleophile, making a nucleophilic attack on beta-lactam ring, to form acyl-enzyme intermediate. According to the early studies ([1], [3], [4] & [5]), Tyr150 was considered to function as general acid-base. In contrast, the more recent report, [22], suggested substrate-assisted base. In this reported mechanism, C4' carboxylate of the substrate may activate Tyr150, which in turn may activate Ser64 by abstracting a proton from the serine residue during the acylation step [22]. Lys67 might play an intermediary role in transfer of the proton [22]. In the next deacylation step, a water molecule bound to Thr316 (and possibly Tyr150) makes an attack on the C8 carbonyl carbon of the acyl-enzyme intermediate, activating the Ser64 to be a leaving group [22]. The role of Tyr150 seems to be still controversial. However, considering the structure with ligand, Ser64, Tyr150, and Lys150 act as a nucleophile, acid-base, and a modulator for acid-base. Here, mainchain amide groups of Ser64 and Ser318 form an oxyanion hole. These suggest that the mechanism is very similar to that of trypsin (D00197).