Molecular evolution of thyroid peroxidase.

Thyroid peroxidase is a member of a family of mammalian peroxidases that includes myeloperoxidase, lactoperoxidase, eosinophil peroxidase, and salivary peroxidase. Protein sequences showing a high degree of sequence similarity with mammalian peroxidases have recently been observed in several invertebrate species. A multiple sequence alignment prepared with five mammalian and six invertebrate peroxidases shows complete conservation of amino acid residues considered to be important in the formation of peroxidase compound 1.

Proximal and distal histidines in thyroid peroxidase: relation to the alternatively spliced form, TPO-2.

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.

Mechanism for the anti-thyroid action of minocycline.

Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated.

Selectivity in tyrosyl iodination sites in human thyroglobulin.

Previous studies indicate that when low iodine thyroglobulin (Tg) is iodinated enzymatically with thyroid peroxidase (TPO), the tyrosyl residues that are used for the formation of thyroid hormone (hormonogenic sites) are selected for early iodination. The aim of the present study was to assess the relative importance of the substrate (Tg) and the enzyme (TPO) in the selection of the early tyrosyl sites that undergo iodination. For this purpose, low iodine human Tg (2.

Minocycline and the thyroid: antithyroid effects of the drug, and the role of thyroid peroxidase in minocycline-induced black pigmentation of the gland.

Minocycline (MN), a member of the tetracycline family of antibiotics, is known to induce a black discoloration of the thyroid in several species, including humans. Antithyroid effects of MN have also been reported. The aim of the present study was two-fold: (1) to determine whether thyroid peroxidase (TPO) is involved in the MN-induced black thyroid, and (2) to obtain information on the effect of MN on TPO-catalyzed iodination and coupling in model systems containing highly purified TPO.