{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:14:11Z","timestamp":1789827251198,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology (DBT) of the Ministry of Science and Technology New Delhi"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Lactoperoxidase (<jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content>, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chem.qmul.ac.uk\/iubmb\/enzyme\/EC1\/11\/1\/7.html\">EC 1.11.1.7<\/jats:ext-link>) is a member of the mammalian heme peroxidase family which also includes thyroid peroxidase (<jats:styled-content style=\"fixed-case\">TPO<\/jats:styled-content>). These two enzymes have a sequence homology of 76%. The structure of <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> is known but not that of <jats:styled-content style=\"fixed-case\">TPO<\/jats:styled-content>. In order to determine the mode of binding of antithyroid drugs to thyroid peroxidase, we have determined the crystal structure of <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> complexed with an antithyroid drug, methimazole (<jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content>) at 1.97 \u00c5 resolution. <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> was isolated from caprine colostrum, purified to homogeneity and crystallized with 20% poly(ethylene glycol)\u20103350. Crystals of <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> were soaked in a reservoir solution containing <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content>. The structure determination showed the presence of two crystallographically independent molecules in the asymmetric unit. Both molecules contained one molecule of <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content>, but with different orientations. <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content> was held tightly between the heme moiety on one side and the hydrophobic parts of the side chains of Arg255, Glu258, and Leu262 on the opposite side. The back of the cleft contained the side chains of Gln105 and His109 which also interacted with <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content>. In both orientations, <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content> had identical buried areas and formed a similar number of interactions. It appears that the molecules of <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content> can enter the substrate\u2010binding channel of <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> in two opposite orientations. But once they reach the distal heme pocket, their orientations are frozen due to equally tight packing of <jats:styled-content style=\"fixed-case\">MMZ<\/jats:styled-content> in both orientations. This is a novel example of an inhibitor binding to an enzyme with two orientations at the same site with nearly equal occupancies.<\/jats:p>","DOI":"10.1002\/2211-5463.12051","type":"journal-article","created":{"date-parts":[[2016,3,12]],"date-time":"2016-03-12T18:26:24Z","timestamp":1457807184000},"page":"640-650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dual binding mode of antithyroid drug methimazole to mammalian heme peroxidases \u2013 structural determination of the lactoperoxidase\u2013methimazole complex at 1.97 \u00c5 resolution"],"prefix":"10.1002","volume":"6","author":[{"given":"Rashmi Prabha","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Biophysics All India Institute of Medical Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biophysics 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