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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
Author(s) -
Martin P.,
Jullien E.,
Courvalin P.
Publication year - 1988
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1988.tb00070.x
Subject(s) - biology , sequence motif , genetics , phosphotransferases , sequence alignment , nucleic acid sequence , gene , biochemistry , conserved sequence , acinetobacter baumannii , peptide sequence , kinase , bacteria , pseudomonas aeruginosa
Summary A new kanamycin‐resistance gene, detected in Acinetobacter baumannii and designated aphA‐6 , was sequenced. It specifiesa 30319 Dalton 3′‐aminoglycosidephospliotransferase (APH(3′)) that mediates resistance to kanamycin and structurally related aminogiycosides, including amikacin. Pairwise comparisons of the six types of APH(3′) so far detected inhuman pathogens (types I, II, IM and VI) and in aminoglycoside‐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 databases for each of these motifs revealed that motifs 1and 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.