1dnu

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spinqualitylabelsall models 1dnu, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURAL ANALYSES OF HUMAN MYELOPEROXIDASE-THIOCYANATE COMPLEX

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Alzheimer disease, susceptibility to OMIM:[606989], Lung cancer, protection against, in smokers OMIM:[606989], Myeloperoxidase deficiency OMIM:[606989]

About this Structure

1DNU is a Protein complex structure of sequences from Homo sapiens with NAG, CA, SCN, SO4, HEM and ACY as ligands. Active as Peroxidase, with EC number 1.11.1.7 Full crystallographic information is available from OCA.

Reference

Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution., Blair-Johnson M, Fiedler T, Fenna R, Biochemistry. 2001 Nov 20;40(46):13990-7. PMID:11705390

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