title: Proximal and distal histidines in thyroid peroxidase: relation to the alternatively spliced form, TPO-2.
abstract: The distal and proximal histidines in thyroid peroxidase (TPO), located by amino acid sequence alignment with their known counterparts in myeloperoxidase, are His 239 and His 494, respectively. These histidines lie outside the 57 amino acid peptide (residues 533-589) that is absent in the alternatively spliced form, TPO-2. However, asparagine 579, which very likely forms a stabilizing hydrogen bond with the proximal histidine in TPO, lies within the missing peptide region. The absence of Asn 579 from TPO-2 may be at least partially responsible for the reported lack of activity of this form of the enzyme. Formation of TPO compound I may also depend on Arg 396, based on analogy with the catalytic mechanism previously proposed for the more widely studied plant and fungal peroxidases. A multiple sequence alignment prepared with five mammalian and five invertebrate peroxidases shows complete conservation of Arg 396, as well as residues corresponding to His 239, His 494, and Asn 579 in TPO. The animal peroxidases comprise a family of homologous proteins that differ markedly from the plant/fungal/bacterial peroxidases in primary, secondary, and tertiary structure, yet share with them a common function. Animal peroxidases probably arose independently of the plant/fungal/bacterial peroxidase superfamily and most likely belong to a different gene family. The relation between animal and nonanimal peroxidases may represent an example of convergent evolution to a common enzymatic mechanism.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041, USA.
authors.forename: A
authors.initials: A
authors.lastname: Taurog
authors.forename: M
authors.initials: M
authors.lastname: Wall
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D006639:Histidine / Q000235:genetics*; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D006639:Histidine; D007453:Iodide Peroxidase