Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases
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UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
1997-06-13Keywords
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
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
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.Source
Cell. 1997 Jun 13;89(6):887-95. doi:10.1016/S0092-8674(00)80274-3DOI
10.1016/S0092-8674(00)80274-3Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50092Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/S0092-8674(00)80274-3