Biomaterial Database

Chemical anatomy of antibiotic resistance: chloramphenicol acetyltransferase. 1992

W V Shaw

Department of Biochemistry, University of Leicester, U.K.

The evolution of mechanisms of resistance to natural antimicrobial substances (antibiotics) was almost certainly concurrent with the development in microorganisms of the ability to synthesise such agents. Of the several general strategies adopted by bacteria for defence against antibiotics, one of the most pervasive is that of enzymic inactivation. The vast majority of eubacteria that are resistant to chloramphenicol, an inhibitor of prokaryotic protein synthesis, owe their resistance phenotype to genes for chloramphenicol acetyltransferase (CAT), which catalyses O-acetylation of the antibiotic, using acetyl-CoA as the acyl donor. The structure of CAT is known, as are many of the properties of the enzyme which explain its remarkable specificity and catalytic efficiency. Less clear is the evolutionary pathway which has produced the different members of the CAT 'family' of enzymes. Hints come from other acetyltransferases which share structure and mechanistic features with CAT, while not being strictly 'homologous' at the level of amino acid sequence. The 'super-family' of trimeric acetyltransferases appears to have in common a chemical mechanism based on a shared architecture.

UI	MeSH Term	Description	Entries
D008956	Models, Chemical	Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Chemical Models,Chemical Model,Model, Chemical
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
D002702	Chloramphenicol Resistance	Nonsusceptibility of bacteria to the action of CHLORAMPHENICOL, a potent inhibitor of protein synthesis in the 50S ribosomal subunit where amino acids are added to nascent bacterial polypeptides.	Chloramphenicol Resistances
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001419	Bacteria	One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.	Eubacteria
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D015500	Chloramphenicol O-Acetyltransferase	An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.	CAT Enzyme,Chloramphenicol Acetyltransferase,Chloramphenicol Transacetylase,Acetyltransferase, Chloramphenicol,Chloramphenicol O Acetyltransferase,Enzyme, CAT,O-Acetyltransferase, Chloramphenicol,Transacetylase, Chloramphenicol
D016415	Sequence Alignment	The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.	Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations