Title

Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

6-13-1997

Document Type

Article

Medical Subject Headings

Aminoglycosides; *Anti-Bacterial Agents; Binding Sites; Crystallography; *Drug Resistance, Microbial; Enterococcus; Eukaryotic Cells; Kanamycin Kinase; Molecular Sequence Data; Phosphotransferases (Alcohol Group Acceptor); Protein Kinases; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Signal Transduction; Staphylococcus

Disciplines

Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics

Abstract

Bacterial resistance to aminoglycoside antibiotics is almost exclusively accomplished through either phosphorylation, adenylylation, or acetylation of the antibacterial agent. The aminoglycoside kinase, APH(3')-IIIa, catalyzes the phosphorylation of a broad spectrum of aminoglycoside antibiotics. The crystal structure of this enzyme complexed with ADP was determined at 2.2 A. resolution. The three-dimensional fold of APH(3')-IIIa reveals a striking similarity to eukaryotic protein kinases despite a virtually complete lack of sequence homology. Nearly half of the APH(3')-IIIa sequence adopts a conformation identical to that seen in these kinases. Substantial differences are found in the location and conformation of residues presumably responsible for second-substrate specificity. These results indicate that APH(3') enzymes and eukaryotic-type protein kinases share a common ancestor.

Rights and Permissions

Citation: Cell. 1997 Jun 13;89(6):887-95. doi:10.1016/S0092-8674(00)80274-3

Comments

At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed