1cxp
From Proteopedia
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|PDB= 1cxp |SIZE=350|CAPTION= <scene name='initialview01'>1cxp</scene>, resolution 1.80Å | |PDB= 1cxp |SIZE=350|CAPTION= <scene name='initialview01'>1cxp</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1d2v|1D2V]], [[1mhl|1MHL]], [[1myp|1MYP]], [[1d5l|1D5L]], [[1d7w|1D7W]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cxp OCA], [http://www.ebi.ac.uk/pdbsum/1cxp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1cxp RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239). Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336). Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide. Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase. It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2)O(2) for access to the distal histidine, whereas in compound I, the same site may be the halide substrate-binding site. | The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239). Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336). Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide. Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase. It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2)O(2) for access to the distal histidine, whereas in compound I, the same site may be the halide substrate-binding site. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Alzheimer disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606989 606989]], Lung cancer, protection against, in smokers OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606989 606989]], Myeloperoxidase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606989 606989]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Fenna, R E.]] | [[Category: Fenna, R E.]] | ||
[[Category: Fiedler, T J.]] | [[Category: Fiedler, T J.]] | ||
| - | [[Category: ACT]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: NAG]] | ||
| - | [[Category: SO4]] | ||
[[Category: heme-protein]] | [[Category: heme-protein]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
[[Category: peroxidase]] | [[Category: peroxidase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:30:38 2008'' |
Revision as of 16:30, 30 March 2008
| |||||||
| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , , , , , | ||||||
| Activity: | Peroxidase, with EC number 1.11.1.7 | ||||||
| Related: | 1D2V, 1MHL, 1MYP, 1D5L, 1D7W
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYOGENIC CRYSTAL STRUCTURE OF HUMAN MYELOPEROXIDASE ISOFORM C
Overview
The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239). Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336). Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide. Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase. It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2)O(2) for access to the distal histidine, whereas in compound I, the same site may be the halide substrate-binding site.
About this Structure
1CXP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution., Fiedler TJ, Davey CA, Fenna RE, J Biol Chem. 2000 Apr 21;275(16):11964-71. PMID:10766826
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