Evolutionary conservation of biotinidase: implications for the enzyme's structure and subcellular localization.
Biotinidases from various species ranging from fungi and insects to human have specific amino acids, and regions that are evolutionarily conserved. These specific amino acids and regions are further supported by their homology to a variety of amidases and nitrilases and by the location of missense mutations that cause biotinidase deficiency in humans. Glu-Lys-Cys residues from three of these regions are considered the catalytic triad involved in the catalysis of the amide linkage. The last one-third of the biotinidase sequence is lacking in nitrilases-amidases, which do not bind biocytin or biotin, therefore, it is likely that the biocytin-biotin-binding site of biotinidase is within this portion of the molecule. Although there are many missense mutations at the far C-terminus of the enzyme, the function of this region is still unclear. Biotinidase may have different functions in different cells or in different subcellular compartments. Using computer programs that predict the subcellular localization of proteins based on their N-terminal signal peptides, microsomal localization resulting in secretion was predicted for biotinidase from all species, whereas there is little consistent support for mitochondrial or nuclear localization of the enzymes. Additional immunohistochemical studies of various human tissues at different stages of development are necessary to resolve the ambiguity of subcellular localization of biotinidase.
Wolf
Barry
B
Department of Pediatrics, Connecticut Children's Medical Center, Hartford, CT, USA. bwolf@ccmckids.org
Jensen
Kevin
K
D000595:Amino Acid Sequence; D000818:Animals; D043523:Biotinidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013347:Subcellular Fractions / Q000378:metabolism*
D043523:Biotinidase