1D2V

CRYSTAL STRUCTURE OF BROMIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5

Summary for 1D2V

• Entry DOI: 10.2210/pdb1d2v/pdb
• Related: 1CXP 1MHL 1MYP
• Descriptor: MYELOPEROXIDASE, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, BROMIDE ION, ... (10 entities in total)
• Functional Keywords: heme-protein, peroxidase, oxidoreductase, peroxidase-bromide complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 135868.64

Authors

Fiedler, T.J.,Davey, C.A.,Fenna, R.E. (deposition date: 1999-09-28, release date: 2000-04-24, Last modification date: 2024-12-25)

Primary citation

Fiedler, T.J.,Davey, C.A.,Fenna, R.E.
X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution.
J.Biol.Chem., 275:11964-11971, 2000

PubMed Abstract: The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239). Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336). Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide. Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase. It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2)O(2) for access to the distal histidine, whereas in compound I, the same site may be the halide substrate-binding site.

PubMed: 10766826
DOI: 10.1074/jbc.275.16.11964

Experimental method

X-RAY DIFFRACTION (1.75 Å)