3BXI

Structure of the complex of bovine lactoperoxidase with its catalyzed product hypothiocyanate ion at 2.3A resolution

Summary for 3BXI

• Entry DOI: 10.2210/pdb3bxi/pdb
• Related: 1CXP 2OJV
• Descriptor: Lactoperoxidase, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: peroxidase, heme, antibacterial, antibiotic, antimicrobial, glycoprotein, hydrogen peroxide, iron, metal-binding, oxidoreductase, secreted
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 1
• Total formula weight: 70978.96

Authors

Singh, A.K.,Singh, N.,Sharma, S.,Shin, K.,Takase, M.,Kaur, P.,Srinivasan, A.,Singh, T.P. (deposition date: 2008-01-14, release date: 2008-03-25, Last modification date: 2024-10-16)

Primary citation

Singh, A.K.,Singh, N.,Sharma, S.,Shin, K.,Takase, M.,Kaur, P.,Srinivasan, A.,Singh, T.P.
Inhibition of lactoperoxidase by its own catalytic product: crystal structure of the hypothiocyanate-inhibited bovine lactoperoxidase at 2.3-A resolution.
Biophys.J., 96:646-654, 2009

PubMed Abstract: To 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.

PubMed: 19167310
DOI: 10.1016/j.bpj.2008.09.019

Experimental method

X-RAY DIFFRACTION (2.3 Å)