An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins.
The functionally diverse actin, hexokinase, and hsp70 protein families have in common an ATPase domain of known three-dimensional structure. Optimal superposition of the three structures and alignment of many sequences in each of the three families has revealed a set of common conserved residues, distributed in five sequence motifs, which are involved in ATP binding and in a putative interdomain hinge. From the multiple sequence alignment in these motifs a pattern of amino acid properties required at each position is defined. The discriminatory power of the pattern is in part due to the use of several known three-dimensional structures and many sequences and in part to the "property" method of generalizing from observed amino acid frequencies to amino acid fitness at each sequence position. A sequence data base search with the pattern significantly matches sugar kinases, such as fuco-, glucono-, xylulo-, ribulo-, and glycerokinase, as well as the prokaryotic cell cycle proteins MreB, FtsA, and StbA. These are predicted to have subdomains with the same tertiary structure as the ATPase subdomains Ia and IIa of hexokinase, actin, and Hsc70, a very similar ATP binding pocket, and the capacity for interdomain hinge motion accompanying functional state changes. A common evolutionary origin for all of the proteins in this class is proposed.
Bork
P
P
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Sander
C
C
Valencia
A
A
D000199:Actins / Q000737:chemistry / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002453:Cell Cycle; D004926:Escherichia coli / Q000235:genetics; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics*; D006593:Hexokinase / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor); D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
D000199:Actins; D006360:Heat-Shock Proteins; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); D006593:Hexokinase; C032700:xylulokinase; D000251:Adenosine Triphosphatases