title: Conservation of biotindase in mammals and identification of the putative biotinidase gene in Drosophila melanogaster.
abstract: Biotinidase deficiency is an autosomal recessively inherited disorder that is characterized by the failure to recycle biotin. Many of the known mutations that cause profound biotinidase deficiency are due to missense mutations that alter amino acids that are presumably important for proper enzyme function. Amino acids essential for biotinidase activity are likely conserved in species that are dependent on biotin recycling. To gain further insight into those amino acids or regions of biotinidase that are important for enzyme activity, we examined the conservation of the amino acids in various mammalian species. The amino acid sequences of biotinidase of monkey, cow, mouse, rat, and pig from the second putative transcription start site to the stop codon of the proteins are highly conserved when compared with each other and with human enzyme, but regions upstream of the second putative transcription start site are not conserved. In addition, because the entire genome of Drosophila is now available, we have identified the putative biotinidase gene in the insect and its corresponding amino acid sequence. The same 62-amino-acid region, which includes a cysteine and is an essential part of the active site of bacterial amidases and nitrilases, is highly conserved in all the mammalian and putative Drosophila biotinidases. Many of the missense mutations that cause biotinidase deficiency are located in these conserved regions of the mammalian and Drosophila biotinidases.
authors.affiliation: Department of Human Genetics, Medical College of Virigina of Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Swango
authors.forename: B
authors.initials: B
authors.lastname: Wolf
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D043523:Biotinidase; D002417:Cattle; D002645:Chickens; D017124:Conserved Sequence; D017931:DNA Primers; D030541:Databases, Genetic; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D016133:Polymerase Chain Reaction; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013552:Swine
chemical_list: D017931:DNA Primers; D000581:Amidohydrolases; D043523:Biotinidase