Biomaterial Database

An engineered Staphylococcus aureus PC1 beta-lactamase that hydrolyses third-generation cephalosporins. 1995

L E Zawadzke, and T J Smith, and O Herzberg

Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville 20850, USA.

The beta-lactamase from Staphylococcus aureus PC1 has been cloned into an Escherichia coli vector for site-directed mutagenesis and high-level protein expression. A mutant enzyme has been produced in which Ala238 is replaced by a serine, and Ile239 is deleted (A238S:I239del). The engineered enzyme hydrolyses third-generation cephalosporins substantially more rapidly than the parental enzyme does, while hydrolysis of benzylpenicillin is slower with the mutant than with the wild-type and native enzymes. The mutant beta-lactamase has been crystallized and the structure determined and refined at 2.8 A resolution. The disposition of the beta-strand which forms the side of the active site is altered in comparison with the native S. aureus beta-lactamase structure, widening the active site cleft and providing space to accommodate the bulky side-chains of the third-generation cephalosporins.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002439	Cefotaxime	Semisynthetic broad-spectrum cephalosporin.	Benaxima,Biosint,Cefotaxim,Cefotaxime Sodium,Cefradil,Cephotaxim,Claforan,Fotexina,HR-756,Kendrick,Klaforan,Primafen,Ru-24756,Taporin,HR 756,HR756,Ru 24756,Ru24756,Sodium, Cefotaxime
D002442	Ceftazidime	Semisynthetic, broad-spectrum antibacterial derived from CEPHALORIDINE and used especially for Pseudomonas and other gram-negative infections in debilitated patients.	Ceftazidime Anhydrous,Ceftazidime Pentahydrate,Fortaz,Fortum,GR-20263,LY-139381,Pyridinium, 1-((7-(((2-amino-4-thiazolyl)((1-carboxy-1-methylethoxy)imino)acetyl)amino)-2-carboxy-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-3-yl)methyl)-, inner salt, pentahydrate, (6R-(6alpha,7beta(Z)))-,Tazidime,GR 20263,GR20263,LY 139381,LY139381
D002509	Cephaloridine	A cephalosporin antibiotic.	Cefaloridine,Cephalomycine,Cephaloridin,Ceporin
D002511	Cephalosporins	A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.	Antibiotics, Cephalosporin,Cephalosporanic Acid,Cephalosporin,Cephalosporin Antibiotic,Cephalosporanic Acids,Acid, Cephalosporanic,Acids, Cephalosporanic,Antibiotic, Cephalosporin,Cephalosporin Antibiotics
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004926	Escherichia coli	A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.	Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli