Protein Science, Vol 9, Issue 12 2344-2353, Copyright © 2000 by Cold Spring Harbor Laboratory Press

JOURNAL ARTICLE

Functional prediction: identification of protein orthologs and paralogs

R Chen and SS Jeong
Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Canada. ridong.chen@monsanto.com

Orthologs typically retain the same function in the course of evolution. Using beta-decarboxylating dehydrogenase family as a model, we demonstrate that orthologs can be confidently identified. The strategy is based on our recent findings that substitutions of only a few amino acid residues in these enzymes are sufficient to exchange substrate and coenzyme specificities. Hence, the few major specificity determinants can serve as reliable markers for determining orthologous or paralogous relationships. The power of this approach has been demonstrated by correcting similarity-based functional misassignment and discovering new genes and related pathways, and should be broadly applicable to other enzyme families.
CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Aoshima and Y. Igarashi Nondecarboxylating and Decarboxylating Isocitrate Dehydrogenases: Oxalosuccinate Reductase as an Ancestral Form of Isocitrate Dehydrogenase J. Bacteriol., March 15, 2008; 190(6): 2050 - 2055. [Abstract] [Full Text] [PDF]

				J. Miyazaki, K. Asada, S. Fushinobu, T. Kuzuyama, and M. Nishiyama Crystal Structure of Tetrameric Homoisocitrate Dehydrogenase from an Extreme Thermophile, Thermus thermophilus: Involvement of Hydrophobic Dimer-Dimer Interaction in Extremely High Thermotolerance J. Bacteriol., October 1, 2005; 187(19): 6779 - 6788. [Abstract] [Full Text] [PDF]

				S. Watanabe, Y. Yasutake, I. Tanaka, and Y. Takada Elucidation of stability determinants of cold-adapted monomeric isocitrate dehydrogenase from a psychrophilic bacterium, Colwellia maris, by construction of chimeric enzymes Microbiology, April 1, 2005; 151(4): 1083 - 1094. [Abstract] [Full Text] [PDF]

				Y. Yasutake, S. Watanabe, M. Yao, Y. Takada, N. Fukunaga, and I. Tanaka Crystal Structure of the Monomeric Isocitrate Dehydrogenase in the Presence of NADP+: INSIGHT INTO THE COFACTOR RECOGNITION, CATALYSIS, AND EVOLUTION J. Biol. Chem., September 19, 2003; 278(38): 36897 - 36904. [Abstract] [Full Text] [PDF]

				J. Miyazaki, N. Kobashi, M. Nishiyama, and H. Yamane Characterization of Homoisocitrate Dehydrogenase Involved in Lysine Biosynthesis of an Extremely Thermophilic Bacterium, Thermus thermophilus HB27, and Evolutionary Implication of beta -Decarboxylating Dehydrogenase J. Biol. Chem., January 10, 2003; 278(3): 1864 - 1871. [Abstract] [Full Text] [PDF]

				I. H. Steen, D. Madern, M. Karlstrom, T. Lien, R. Ladenstein, and N.-K. Birkeland Comparison of Isocitrate Dehydrogenase from Three Hyperthermophiles Reveals Differences in Thermostability, Cofactor Specificity, Oligomeric State, and Phylogenetic Affiliation J. Biol. Chem., November 16, 2001; 276(47): 43924 - 43931. [Abstract] [Full Text] [PDF]