5ff1

Two way mode of binding of antithyroid drug methimazole to mammalian heme peroxidases: Structure of the complex of lactoperoxidase with methimazole at 1.97 Angstrom resolution

spinqualitylabelsall models 5ff1, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ff1 is a 2 chain structure with sequence from Capra hircus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.97Å Ligands: CA, GOL, HEM, MMZ, NAG, NO3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PERL_CAPHI Antimicrobial agent which utilizes hydrogen peroxide and thiocyanate (SCN) to generate the antimicrobial substance hypothiocyanous acid (HOSCN) (PubMed:10894086). May protect the udder from infection and promote growth in newborns. Inhibits growth of several fungi including A.niger, Trichoderma species, C.cassicola, P.meadii and C.salmonicolor (PubMed:10894086). Does not have anti-fungal activity towards C.albicans and Pythium species (PubMed:10894086). Inhibits growth of several Gram-positive bacteria including some Staphylococcus species and Gram-negative bacteria including E.coli, P.aeruginosa and some Salmonella species (PubMed:10894086). Publication Abstract from PubMed 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 A 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, but with different orientations. MMZ 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 MMZ. In both orientations, MMZ had identical buried areas and formed a similar number of interactions. It appears that the molecules of MMZ can enter the substrate-binding channel of LPO in two opposite orientations. But once they reach the distal heme pocket, their orientations are frozen due to equally tight packing of MMZ 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. Dual binding mode of antithyroid drug methimazole to mammalian heme peroxidases - structural determination of the lactoperoxidase-methimazole complex at 1.97 A resolution.,Singh RP, Singh A, Sirohi HV, Singh AK, Kaur P, Sharma S, Singh TP FEBS Open Bio. 2016 Jun 14;6(7):640-50. doi: 10.1002/2211-5463.12051. eCollection, 2016 Jul. PMID:27398304 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lactoperoxidase

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