Title
Aminoglycoside phosphotransferases: proteins, structure, and mechanism
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
1999-01-01
Document Type
Article
Subjects
Aminoglycosides; Anti-Bacterial Agents; Drug Resistance, Microbial; Evolution, Molecular; Gram-Negative Bacteria; Gram-Positive Bacteria; *Kanamycin Kinase; inhibitors; Models, Molecular; Mycobacterium; Protein Conformation; Substrate Specificity; Terminology as Topic
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
Abstract
Aminoglycoside antibiotics constitute an important class of clinically useful drugs which are imperiled by the emergence of resistant organisms. Aminoglycoside resistance in the clinics is primarily due to the presence of modifying enzymes which N-acetylate, O-adenylate or O-phosphorylate the antibiotics. The latter family of enzymes are termed the aminoglycoside phosphotransferases or kinases and are the subject of this review. There are seven classes of aminoglycoside phosphotransferases (APH(3'), APH(2''), APH(3'off'), APH(6), APH(9), APH(4), APH(7'')) and many isozymes in each class, and although there is very little overall general sequence homology among these enzymes, certain signature residues and sequences are common. The recent determination of the three-dimensional structure of the broad spectrum aminoglycoside kinase APH(3')-IIIa complexed with the product ADP, in addition to mechanistic and mutagenic studies on this and related enzymes, has added a great deal to our understanding of this class of antibiotic resistance enzyme. In particular, the revelation of structural and mechanistic similarities between APHs and Ser/Thr and Tyr kinases has set the stage for future inhibition studies which could prove important in reversing aminoglycoside resistance.
Source
Front Biosci. 1999 Jan 1;4:D9-21.
Journal/Book/Conference Title
Frontiers in bioscience : a journal and virtual library
Related Resources
Repository Citation
Wright GD, Thompson PR. (1999). Aminoglycoside phosphotransferases: proteins, structure, and mechanism. Thompson Lab Publications. Retrieved from https://escholarship.umassmed.edu/thompson/94
Comments
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.