Homology analysis of the protein sequences of fatty acid synthases from chicken liver, rat mammary gland, and yeast.
Homology analyses of the protein sequences of chicken liver and rat mammary gland fatty acid synthases [acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester hydrolyzing), EC 2.3.1.85] and yeast fatty acid synthase [fatty-acyl-CoA synthase; acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing), EC 2.3.1.86] were carried out. The amino acid sequences of the chicken and rat enzymes are 67% identical. If conservative substitutions are allowed, 78% of the amino acids are matched. A region of low homologies exists between the functional domains, in particular around amino acid residues 1059-1264 of the chicken enzyme. Homologies between the active sites of chicken and rat and of chicken and yeast enzymes have been analyzed by an alignment method. A high degree of homology exists between the active sites of the chicken and rat enzymes. However, the chicken and yeast enzymes show a lower degree of homology. The NADPH-binding dinucleotide folds of the beta-ketoacyl reductase and the enoyl reductase sites were identified by comparison with a known consensus sequence for the NADP- and FAD-binding dinucleotide folds. The active sites of all of the enzymes are primarily in hydrophobic regions of the protein. This study suggests that the genes for the functional domains of fatty acid synthase were originally separated, and these genes were connected to each other by using different connecting nucleotide sequences in different species. An alternative explanation for the differences in rat and chicken is a common ancestry and mutations in the joining regions during evolution. A higher mutation rate in the joining regions than in the active site regions of the enzymes without loss of function might be expected.
Chang
S I
SI
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115.
Hammes
G G
GG
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D064429:Fatty Acid Synthases / Q000235:genetics*; D005260:Female; D008099:Liver / Q000201:enzymology*; D008321:Mammary Glands, Animal / Q000201:enzymology*; D008969:Molecular Sequence Data; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D012689:Sequence Homology, Nucleic Acid
D064429:Fatty Acid Synthases