Nucleotide sequence of Acinetobacter baumannii aphA-6 gene: evolutionary and functional implications of sequence homologies with nucleotide-binding proteins, kinases and other aminoglycoside-modifying enzymes. 1988

P Martin, and E Jullien, and P Courvalin
Unité des Agents Antibactériens, CNRS UA 271, Paris, France.

A new kanamycin-resistance gene, detected in Acinetobacter baumannii and designated aphA-6, was sequenced. It specifies a 30319 Dalton 3'-aminoglycoside phosphotransferase (APH(3'] that mediates resistance to kanamycin and structurally related aminoglycosides, including amikacin. Pairwise comparisons of the six types of APH(3') so far detected in human pathogens (types I, II, III and VI) and in amino-glycoside-producing microorganisms (types IV and V), confirm that APH(3') enzymes have diverged from a common ancestor. Three highly retained motifs (1: V--HGD----N; 2: G--D-GR/K-G and 3: D--K/R--Y/F---LDE) located in the C-terminal part of the enzymes were defined. Screening of protein sequence data bases fore each of these motifs revealed that motifs 1 and 2 are both found in nucleotide-binding phosphotransferases associated with a variety of biological processes, namely adenylate kinase, viral oncogenic protein kinases, elongation factors, Na+/K+-transporting ATPase, myosin and antibiotic-modifying enzymes. Motif 2 probably corresponds to the MgATP binding site, while motifs 3 and 1 could be involved in the splitting of the phosphodiester bond and in the phosphate transfer, respectively. Moreover, an additional motif, almost invariably centrally located, was found in all aminoglycoside-modifying enzymes. The occurrence of this motif, possibly a recombination site which would have allowed the association of units of separate functions, is compatible with a modular concept for the structure of aminoglycoside-modifying enzymes.

UI MeSH Term Description Entries
D007613 Kanamycin Resistance Nonsusceptibility of bacteria to the antibiotic KANAMYCIN, which can bind to their 70S ribosomes and cause misreading of messenger RNA.
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
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010770 Phosphotransferases A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7. Kinases,Phosphotransferase,Phosphotransferases, ATP,Transphosphorylase,Transphosphorylases,Kinase,ATP Phosphotransferases
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002373 Cyclic AMP Receptor Protein A transcriptional regulator in prokaryotes which, when activated by binding cyclic AMP, acts at several promoters. Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. Cell surface cyclic AMP receptors are not included (CYCLIC AMP RECEPTORS), nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins, which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES. Catabolic Gene Activators,Catabolite Activator Protein,Catabolite Gene Activator Protein,Catabolite Gene Activator Proteins,Activator Protein, Catabolite,Activator Proteins, Catabolite,Activator, Catabolic Gene,Activators, Catabolic Gene,Catabolic Gene Activator,Catabolite Activator Proteins,Catabolite Regulator Protein,Catabolite Regulator Proteins,Cyclic AMP Receptor Proteins,Gene Activator, Catabolic,Gene Activators, Catabolic,Protein, Catabolite Activator,Protein, Catabolite Regulator,Proteins, Catabolite Activator,Proteins, Catabolite Regulator,Regulator Protein, Catabolite,Regulator Proteins, Catabolite,cAMP Receptor Protein,cAMP Receptor Proteins,Protein, cAMP Receptor,Proteins, cAMP Receptor,Receptor Protein, cAMP,Receptor Proteins, cAMP
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
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
D005075 Biological Evolution The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics. Evolution, Biological
D005798 Genes, Bacterial The functional hereditary units of BACTERIA. Bacterial Gene,Bacterial Genes,Gene, Bacterial

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