3bxi
Structure of the complex of bovine lactoperoxidase with its catalyzed product hypothiocyanate ion at 2.3A resolution
Structural highlights
FunctionPERL_BOVIN LPO is an antimicrobial agent. It is thought to help protect the udder from infection and promote growth in newborn calves. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTo the best of our knowledge, this is the first report on the structure of product-inhibited mammalian peroxidase. Lactoperoxidase is a heme containing an enzyme that catalyzes the inactivation of a wide range of microorganisms. In the presence of hydrogen peroxide, it preferentially converts thiocyanate ion into a toxic hypothiocyanate ion. Samples of bovine lactoperoxidase containing thiocyanate (SCN(-)) and hypothiocyanate (OSCN(-)) ions were purified and crystallized. The structure was determined at 2.3-A resolution and refined to R(cryst) and R(free) factors of 0.184 and 0.221, respectively. The determination of structure revealed the presence of an OSCN(-) ion at the distal heme cavity. The presence of OSCN(-) ions in crystal samples was also confirmed by chemical and spectroscopic analysis. The OSCN(-) ion interacts with the heme iron, Gln-105 N(epsilon1), His-109 N(epsilon2), and a water molecule W96. The sulfur atom of the OSCN(-) ion forms a hypervalent bond with a nitrogen atom of the pyrrole ring D of the heme moiety at an S-N distance of 2.8 A. The heme group is covalently bound to the protein through two ester linkages involving carboxylic groups of Glu-258 and Asp-108 and the modified methyl groups of pyrrole rings A and C, respectively. The heme moiety is significantly distorted from planarity, whereas pyrrole rings A, B, C, and D are essentially planar. The iron atom is displaced by approximately 0.2 A from the plane of the heme group toward the proximal site. The substrate channel resembles a long tunnel whose inner walls contain predominantly aromatic residues such as Phe-113, Phe-239, Phe-254, Phe-380, Phe-381, Phe-422, and Pro-424. A phosphorylated Ser-198 was evident at the surface, in the proximity of the calcium-binding channel. Inhibition of lactoperoxidase by its own catalytic product: crystal structure of the hypothiocyanate-inhibited bovine lactoperoxidase at 2.3-A resolution.,Singh AK, Singh N, Sharma S, Shin K, Takase M, Kaur P, Srinivasan A, Singh TP Biophys J. 2009 Jan;96(2):646-54. PMID:19167310[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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