Dual binding mode of antithyroid drug methimazole to mammalian heme peroxidases - structural determination of the lactoperoxidase-methimazole complex at 1.97 A resolution.

ABSTRACT: Lactoperoxidase (LPO, EC 1.11.1.7) is a member of the mammalian heme peroxidase family which also includes thyroid peroxidase (TPO). These two enzymes have a sequence homology of 76%. The structure of LPO is known but not that of TPO. In order to determine the mode of binding of antithyroid drugs to thyroid peroxidase, we have determined the crystal structure of LPO complexed with an antithyroid drug, methimazole (MMZ) at 1.97 Å resolution. LPO was isolated from caprine colostrum, purified to homogeneity and crystallized with 20% poly(ethylene glycol)-3350. Crystals of LPO were soaked in a reservoir solution containing MMZ. The structure determination showed the presence of two crystallographically independent molecules in the asymmetric unit. Both molecules contained one molecule of MMZ,

SUBMITTER: Singh RP 

PROVIDER: S-EPMC4932444 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature