Evolutionary relationship between the bacterial HPr kinase and the ubiquitous PEP-carboxykinase: expanding the P-loop nucleotidyl transferase superfamily.
Similarities between protein three-dimensional structures can reveal evolutionary and functional relationships not apparent from sequence comparison alone. Here we report such a similarity between the metabolic enzymes histidine phosphocarrier protein kinase (HPrK) and phosphoenolpyruvate carboxykinase (PCK), suggesting that they are evolutionarily related. Current structure classifications place PCK and other P-loop containing nucleotidyl-transferases into different folds. Our comparison of both HPrK and PCK to other P-loop containing proteins reveals that all share a common structural motif consisting of an alphabeta segment containing the P-loop flanked by an additional beta-strand that is adjacent in space, but far apart along the sequence. Analysis also shows that HPrK/PCK differ from other P-loop containing structures no more than they differ from each other. We thus suggest that HPrK and PCK should be classified with other P-loop containing proteins, and that all probably share a common ancestor that probably contained a simple P-loop motif with different protein segments being added or lost over the course of evolution. We used the structure-based sequence alignment containing residues specific to HPrK/PCK to identify additional members of this P-loop containing family.
Russell
Robert B
RB
Structural and Computational Biology Programme, EMBL, Heidelberg, Germany. russell@embl-heidelberg.de
Márquez
José Antonio
JA
Hengstenberg
Wolfgang
W
Scheffzek
Klaus
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D019143:Evolution, Molecular; D005658:Fungi / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; C110847:HPr kinase; D017346:Protein Serine-Threonine Kinases; D009713:Nucleotidyltransferases; D019764:Phosphoenolpyruvate Carboxykinase (ATP)