Dichotomic Phylogenetic Tree of the Pyruvate Kinase Family: K+-DEPENDENT AND -INDEPENDENT ENZYMES.
K(+) dependence was assumed to be a feature of all pyruvate kinases until it was discovered that some enzymes express K(+) -independent activity. Almost all the K(+)-independent pyruvate kinases have Lys at position 117, instead of the Glu present in the K(+)-dependent muscle enzyme. Mutagenesis studies show that the internal positive charge substitutes for the K(+) requirement (Laughlin, L. T. & Reed, G. H. (1997) Arch. Biochem. Biophys. 348, 262-267). In this work a phylogenetic analysis of pyruvate kinase was performed to ascertain the abundance of K(+) -independent activities and to explore whether the K(+) activating effect is related to the evolutionary history of the enzyme. Of the 230 studied sequences, 46% have Lys at position 117, and the rest have Glu. Pyruvate kinases with Lys(117) and Glu(117) are separated in two clusters. All of the enzymes of the Glu(117) cluster that have been characterized are K(+)-dependent, whereas those of the Lys(117) cluster are K(+)-independent. Thus, there is a strict correlation between the dichotomy of the tree and the dependence of activity on K(+). 77% of the pyruvate kinases that possess Lys(117) have Lys(113)/Gln(114); they also have Ile, Val, or Leu at position 120. These residues are replaced by Glu(117) and Thr(113)/Lys(114)/Thr(120) in 80% of K(+)-dependent pyruvate kinases. Structural analysis indicates that these residues are in a hinge region involved in the acquisition of the catalytic conformation of the enzyme. The route of conversion from K(+)-independent to K(+)-dependent pyruvate kinases is described. A plausible explanation of how enzymes developed K(+) dependence is put forth.[1]References
- Dichotomic Phylogenetic Tree of the Pyruvate Kinase Family: K+-DEPENDENT AND -INDEPENDENT ENZYMES. Oria-Hern??ndez, J., Riveros-Rosas, H., Ram??rez-S??lva, L. J. Biol. Chem. (2006) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
