2uui
From Proteopedia
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| - | [[Image:2uui.gif|left|200px]] | + | [[Image:2uui.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF HUMAN LEUKOTRIENE C4 SYNTHASE''' | + | {{Structure |
| + | |PDB= 2uui |SIZE=350|CAPTION= <scene name='initialview01'>2uui</scene>, resolution 2.00Å | ||
| + | |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene> and <scene name='pdbligand=PLM:PALMITIC ACID'>PLM</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Leukotriene-C(4)_synthase Leukotriene-C(4) synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.20 4.4.1.20] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF HUMAN LEUKOTRIENE C4 SYNTHASE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2UUI is a [ | + | 2UUI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UUI OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase., Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggstrom JZ, Nordlund P, Nature. 2007 Aug 2;448(7153):613-6. Epub 2007 Jul 15. PMID:[http:// | + | Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase., Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggstrom JZ, Nordlund P, Nature. 2007 Aug 2;448(7153):613-6. Epub 2007 Jul 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17632546 17632546] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Leukotriene-C(4) synthase]] | [[Category: Leukotriene-C(4) synthase]] | ||
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[[Category: leukotriene biosynthesis]] | [[Category: leukotriene biosynthesis]] | ||
[[Category: leukotriene signalling]] | [[Category: leukotriene signalling]] | ||
| - | [[Category: | + | [[Category: ltc4]] |
[[Category: lyase]] | [[Category: lyase]] | ||
[[Category: mapeg]] | [[Category: mapeg]] | ||
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[[Category: trimer]] | [[Category: trimer]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:39:52 2008'' |
Revision as of 16:39, 20 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , and | ||||||
| Activity: | Leukotriene-C(4) synthase, with EC number 4.4.1.20 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HUMAN LEUKOTRIENE C4 SYNTHASE
Contents |
Overview
Cysteinyl leukotrienes are key mediators in inflammation and have an important role in acute and chronic inflammatory diseases of the cardiovascular and respiratory systems, in particular bronchial asthma. In the biosynthesis of cysteinyl leukotrienes, conversion of arachidonic acid forms the unstable epoxide leukotriene A4 (LTA4). This intermediate is conjugated with glutathione (GSH) to produce leukotriene C4 (LTC4) in a reaction catalysed by LTC4 synthase: this reaction is the key step in cysteinyl leukotriene formation. Here we present the crystal structure of the human LTC4 synthase in its apo and GSH-complexed forms to 2.00 and 2.15 A resolution, respectively. The structure reveals a homotrimer, where each monomer is composed of four transmembrane segments. The structure of the enzyme in complex with substrate reveals that the active site enforces a horseshoe-shaped conformation on GSH, and effectively positions the thiol group for activation by a nearby arginine at the membrane-enzyme interface. In addition, the structure provides a model for how the omega-end of the lipophilic co-substrate is pinned at one end of a hydrophobic cleft, providing a molecular 'ruler' to align the reactive epoxide at the thiol of glutathione. This provides new structural insights into the mechanism of LTC4 formation, and also suggests that the observed binding and activation of GSH might be common for a family of homologous proteins important for inflammatory and detoxification responses.
Disease
Known disease associated with this structure: Leukotriene C4 synthase deficiency OMIM:[246530]
About this Structure
2UUI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase., Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggstrom JZ, Nordlund P, Nature. 2007 Aug 2;448(7153):613-6. Epub 2007 Jul 15. PMID:17632546
Page seeded by OCA on Thu Mar 20 18:39:52 2008
Categories: Homo sapiens | Leukotriene-C(4) synthase | Single protein | Eshaghi, S. | Haeggstrom, J Z. | Hammarberg, T. | Kohl, A. | Mccarthy, A A. | Molina, D Martinez. | Niegowski, D. | Nordlund, P. | Ohlson, E. | Wetterholm, A. | LMT | NI | PLM | SO4 | Apo | Eicosanoid | Enzyme | Human | Leukotriene biosynthesis | Leukotriene signalling | Ltc4 | Lyase | Mapeg | Membrane | Membrane protein | Transmembrane | Trimer
