1d2v: Difference between revisions
New page: left|200px<br /> <applet load="1d2v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d2v, resolution 1.75Å" /> '''CRYSTAL STRUCTURE O... |
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[[Image:1d2v.gif|left|200px]]<br /> | [[Image:1d2v.gif|left|200px]]<br /><applet load="1d2v" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1d2v, resolution 1.75Å" /> | caption="1d2v, resolution 1.75Å" /> | ||
'''CRYSTAL STRUCTURE OF BROMIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5'''<br /> | '''CRYSTAL STRUCTURE OF BROMIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5'''<br /> | ||
==Overview== | ==Overview== | ||
The x-ray crystal structure of human myeloperoxidase has been extended to | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1D2V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, CA, BR, SO4, ACT and HEM 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:// | 1D2V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=BR:'>BR</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=ACT:'>ACT</scene> and <scene name='pdbligand=HEM:'>HEM</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=1D2V OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Peroxidase]] | [[Category: Peroxidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Davey, C | [[Category: Davey, C A.]] | ||
[[Category: Fenna, R | [[Category: Fenna, R E.]] | ||
[[Category: Fiedler, T | [[Category: Fiedler, T J.]] | ||
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: BR]] | [[Category: BR]] | ||
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[[Category: peroxidase-bromide complex]] | [[Category: peroxidase-bromide complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:12:23 2008'' | ||
Revision as of 13:12, 21 February 2008
|
CRYSTAL STRUCTURE OF BROMIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5
OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
1D2V is a Single protein structure of sequence from Homo sapiens with , , , , and as ligands. Active as Peroxidase, with EC number 1.11.1.7 Full crystallographic information is available from OCA.
ReferenceReference
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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