1DNU

STRUCTURAL ANALYSES OF HUMAN MYELOPEROXIDASE-THIOCYANATE COMPLEX

1DNU の概要

• エントリーDOI: 10.2210/pdb1dnu/pdb
• 関連するPDBエントリー: 1CXP 1D2V 1D5L 1D7W 1DNW 1MHL 1MYP
• 分子名称: 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, THIOCYANATE ION, ... (10 entities in total)
• 機能のキーワード: oxidoreductase, peroxidase, inhibitor complex thiocyanate, halide peroxidation, neutrophil
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 135467.79

構造登録者

Blair-Johnson, M.,Fiedler, T.J.,Fenna, R.E. (登録日: 1999-12-16, 公開日: 2001-12-21, 最終更新日: 2024-12-25)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)