1dnw
From Proteopedia
(New page: 200px<br /> <applet load="1dnw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dnw, resolution 1.90Å" /> '''HUMAN MYELOPEROXIDA...) |
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| - | [[Image:1dnw.gif|left|200px]]<br /> | + | [[Image:1dnw.gif|left|200px]]<br /><applet load="1dnw" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1dnw, resolution 1.90Å" /> | caption="1dnw, resolution 1.90Å" /> | ||
'''HUMAN MYELOPEROXIDASE-CYANIDE-THIOCYANATE COMPLEX'''<br /> | '''HUMAN MYELOPEROXIDASE-CYANIDE-THIOCYANATE COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 1.9 A X-ray crystal structure of human myeloperoxidase complexed with | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DNW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, CA, SCN, SO4, CYN, HEM and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peroxidase Peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.7 1.11.1.7] Full crystallographic information is available from [http:// | + | 1DNW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=SCN:'>SCN</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=CYN:'>CYN</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peroxidase Peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.7 1.11.1.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DNW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Blair-Johnson, M.]] | [[Category: Blair-Johnson, M.]] | ||
| - | [[Category: Fenna, R | + | [[Category: Fenna, R E.]] |
| - | [[Category: Fiedler, T | + | [[Category: Fiedler, T J.]] |
[[Category: ACY]] | [[Category: ACY]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: thiocyanate]] | [[Category: thiocyanate]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:18:32 2008'' |
Revision as of 10:18, 21 February 2008
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HUMAN MYELOPEROXIDASE-CYANIDE-THIOCYANATE COMPLEX
Contents |
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
1DNW is a Protein complex structure of sequences from Homo sapiens with , , , , , and 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
Page seeded by OCA on Thu Feb 21 12:18:32 2008
Categories: Homo sapiens | Peroxidase | Protein complex | Blair-Johnson, M. | Fenna, R E. | Fiedler, T J. | ACY | CA | CYN | HEM | NAG | SCN | SO4 | Halide peroxidation | Oxidoreductase | Substrate complex | Thiocyanate
