1D7W

CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C COMPLEXED WITH CYANIDE AND BROMIDE AT PH 4.0

Summary for 1D7W

• Entry DOI: 10.2210/pdb1d7w/pdb
• Related: 1CXP 1D2V 1D5L 1MHL 1MYP
• Descriptor: MYELOPEROXIDASE, CALCIUM ION, 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, ... (11 entities in total)
• Functional Keywords: heme-protein, peroxidase, oxidoreductase, peroxidase-cyanide-bromide complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 136467.07

Authors

Fiedler, T.J.,Fenna, R.E. (deposition date: 1999-10-20, release date: 2001-12-12, Last modification date: 2020-07-29)

Primary citation

Blair-Johnson, M.,Fiedler, T.,Fenna, R.
Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution.
Biochemistry, 40:13990-13997, 2001

PubMed Abstract: The 1.9 A X-ray crystal structure of human myeloperoxidase complexed with cyanide (R = 0.175, R(free) = 0.215) indicates that cyanide binds to the heme iron with a bent Fe-C-N angle of approximately 157 degrees, and binding is accompanied by movement of the iron atom by 0.2 A into the porphyrin plane. The bent orientation of the cyanide allows the formation of three hydrogen bonds between its nitrogen atom and the distal histidine as well as two water molecules in the distal cavity. The 1.85 A X-ray crystal structure of an inhibitory complex with thiocyanate (R = 0.178, R(free) = 0.210) indicates replacement of chloride at a proximal helix halide binding site in addition to binding in the distal cavity in an orientation parallel with the heme. The thiocyanate replaces two water molecules in the distal cavity and is hydrogen bonded to Gln 91. The 1.9 A structures of the complexes formed by bromide (R = 0.215, R(free) = 0.270) and thiocyanate (R = 0.198, R(free) = 0.224) with the cyanide complex of myeloperoxidase show how the presence of bound cyanide alters the binding site for bromide in the distal heme cavity, while having little effect on thiocyanate binding. These results support a model for a single common binding site for halides and thiocyanate as substrates or as inhibitors near the delta-meso carbon of the porphyrin ring in myeloperoxidase.

PubMed: 11705390
DOI: 10.1021/bi0111808

Experimental method

X-RAY DIFFRACTION (1.9 Å)