1dnu

STRUCTURAL ANALYSES OF HUMAN MYELOPEROXIDASE-THIOCYANATE COMPLEX

spinqualitylabelsall models 1dnu, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1dnu is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACY, BMA, CA, HEM, NAG, SCN, SO4, FUC, MAN NonStd Res: CSO Related: 1d2v, 1mhl, 1myp, 1d5l, 1d7w, 1cxp, 1dnw Activity: Peroxidase, with EC number 1.11.1.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PERM_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. Function [PERM_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 PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Myeloperoxidase Sandbox WWC11

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