title: Molecular phylogenetics of a protein repair methyltransferase.
abstract: Protein-L-isoaspartyl (D-aspartyl) O-methyltransferase (E.C. 2.1.1.77) is a well-conserved and widely distributed protein repair enzyme that methylates isomerized or racemized aspartyl residues in age-damaged proteins. We exploited the availability of protein sequences from 10 diverse animal, plant and bacterial taxa to construct a phylogenetic tree and determine the rates of amino acid substitution for this enzyme. We used a likelihood ratio test to show that this enzyme fulfills the conditions for a molecular clock. We found that the rate of substitution is 0.39 amino acid substitutions per site per 10(9) years and remains relatively constant from bacteria to humans. We argue that this degree of sequence conservation may result from the functional constraints necessitated by the requirement to specifically recognize altered aspartyl but not normal aspartyl residues in proteins. Relative rate analysis of the Caenorhabditis elegans sequence suggests that the amino acid substitution rate in the nematode lineage may be higher than that in other lineages and that the divergence of nematodes may have been a more recent event than suggested by previous analysis.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles 90095-1569, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Kagan
authors.forename: H J
authors.initials: HJ
authors.lastname: McFadden
authors.forename: P N
authors.initials: PN
authors.lastname: McFadden
authors.forename: C
authors.initials: C
authors.lastname: O'Connor
authors.forename: S
authors.initials: S
authors.lastname: Clarke
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D017360:Arabidopsis; D017173:Caenorhabditis elegans; D002417:Cattle; D004331:Drosophila melanogaster; D004926:Escherichia coli; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D011496:Protein Methyltransferases / Q000737:chemistry*; D051381:Rats; D016415:Sequence Alignment; D014908:Triticum
chemical_list: D000596:Amino Acids; D011496:Protein Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase