1mhl
CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C CRYSTALLIZED IN SPACE GROUP P2(1) AT PH 5.5 AND 20 DEG C
Structural highlights
DiseasePERM_HUMAN Defects in MPO are the cause of myeloperoxidase deficiency (MPOD) [MIM:254600. A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis.[1] [2] [3] [4] [5] FunctionPERM_HUMAN Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. 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 PubMedA 3-A-resolution X-ray crystal structure of canine myeloperoxidase has previously revealed the overall structure of the molecule, including the polypeptide backbone conformation, but did not provide an unambiguous structure for the covalently bound heme. A higher resolution (2.28 A) X-ray crystal structure of human myeloperoxidase has now shown that the heme is a novel derivative of protoporphyrin IX in which three ring substituents form covalent bonds with amino acid side chains in the protein. Modified methyl groups on pyrrole rings A and C form ester linkages with glutamate 242 and aspartate 94, while a covalent bond between the vinyl group on ring A and the sulfur atom of methionine 243 results in a sulfonium ion linkage. The heme tetrapyrrole ring also shows considerable distortion from the planar conformation seen in most heme-containing proteins. The observed bending appears to result from these covalent bonds between diametrically opposed pyrrole rings A and C and the protein. Sequence comparisons suggest that the two ester linkages to the heme may also occur in other homologous mammalian peroxidases, but that the sulfonium ion linkage may be a unique feature of myeloperoxidase. Structure of the green heme in myeloperoxidase.,Fenna R, Zeng J, Davey C Arch Biochem Biophys. 1995 Jan 10;316(1):653-6. PMID:7840679[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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