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
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
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DOI：
10.1111/j.1365-2958.1988.tb00070.x
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发表时间：
1988-09-01
影响因子：
3.6
通讯作者：
COURVALIN, P
中科院分区：
文献类型：
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作者：
MARTIN, P;JULLIEN, E;COURVALIN, P
从鲍曼不动杆菌中检测到一个新的卡那霉素耐药基因，命名为aphaA-6。它指定了一个30,319道尔顿3‘-氨基糖苷磷酸转移酶(APH(3“))，它介导卡那霉素和结构上相关的氨基糖苷酶，包括阿米卡星的耐药性。对迄今在人类病原体(I、II、III和VI型)和产生氨基糖苷类微生物(IV和V型)中检测到的六种APH(3‘’)进行配对比较，证实APH(3‘’)酶已从共同祖先中分离出来。在酶的C-末端定义了3个高度保留的基序(1：V--HGD-N；2：G--D-GR/K-G和3：D--K/R--Y/F-LDE)。对每个基序的蛋白质序列数据库的筛选表明，在核苷酸结合的磷酸转移酶中都发现了基序1和2，这些基序与多种生物学过程有关，即腺苷酸激酶、病毒致癌蛋白激酶、延伸因子、Na+/K+转运ATPase、肌球蛋白和抗生素修饰酶。基序2可能对应于镁三磷酸腺苷的结合部位，而基序3和1可能分别参与磷酸二酯键的断裂和磷酸转移。此外，在所有氨基糖苷类修饰酶中都发现了一个几乎总是位于中心的额外基序。这个基序的出现可能是一个重组位点，允许不同功能单位的结合，这与氨基糖苷类修饰酶结构的模块化概念是兼容的。
A new kanamycin-resistance gene, detected in Acinetobacter baumannii and designated aphaA-6, was sequenced. It specifies a 30,319 Dalton 3''-aminoglycoside phosphotransferase (APH(3'')) that mediates resistance to kanamycin and structurally related aminoglycosies, 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 aminoglycoside-producing microorganisms (types IV and V), confirm that APH(3'') enzymes have diverged froma 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 enzyme were defined. Screening of protein sequence data bases for 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.