1v40
From Proteopedia
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|PDB= 1v40 |SIZE=350|CAPTION= <scene name='initialview01'>1v40</scene>, resolution 1.90Å | |PDB= 1v40 |SIZE=350|CAPTION= <scene name='initialview01'>1v40</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=O16:3-(1,3-BENZOTHIAZOL-2-YL)-2-(1,4-DIOXO-1,2,3,4-TETRAHYDROPHTHALAZIN-6-YL)-5-[(E)-2-PHENYLVINYL]-3H-TETRAAZOL-2-IUM'>O16</scene> |
| - | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Prostaglandin-D_synthase Prostaglandin-D synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.99.2 5.3.99.2] </span> | |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1iyh|1IYH]], [[1iyi|1IYI]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1v40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v40 OCA], [http://www.ebi.ac.uk/pdbsum/1v40 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1v40 RCSB]</span> | ||
}} | }} | ||
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[[Category: Uodome, N.]] | [[Category: Uodome, N.]] | ||
[[Category: Urade, Y.]] | [[Category: Urade, Y.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: GSH]] | ||
| - | [[Category: MG]] | ||
| - | [[Category: O16]] | ||
[[Category: gst]] | [[Category: gst]] | ||
[[Category: hematopoietic prostaglandin d synthase]] | [[Category: hematopoietic prostaglandin d synthase]] | ||
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[[Category: sigma-2 class gst]] | [[Category: sigma-2 class gst]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:19:09 2008'' |
Revision as of 21:19, 30 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Prostaglandin-D synthase, with EC number 5.3.99.2 | ||||||
| Related: | 1IYH, 1IYI
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
First Inhibitor Complex Structure of Human Hematopoietic Prostaglandin D Synthase
Overview
Hematopoietic prostaglandin (PG) D synthase (H-PGDS) is responsible for the production of PGD(2) as an allergy or inflammation mediator in mast and Th2 cells. We determined the X-ray structure of human H-PGDS complexed with an inhibitor, 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride (BSPT) at 1.9 A resolution in the presence of Mg(2+). The styryl group of the inhibitor penetrated to the bottom of the active site cleft, and the tetrazole ring was stabilized by the stacking interaction with Trp104, inducing large movement around the alpha5-helix, which caused the space group of the complex crystal to change from P2(1) to P1 upon binding of BSPT. The phthalhydrazidyl group of BSPT exhibited steric hindrance due to the cofactor, glutathione (GSH), increasing the IC(50) value of BSPT for human H-PGDS from 36.2 micro M to 98.1 micro M upon binding of Mg(2+), because the K(m) value of GSH for human H-PGDS was decreased from 0.60 micro M in the presence of EDTA to 0.14 micro M in the presence of Mg(2+). We have to avoid steric hindrance of the GSH molecule that was stabilized by intracellular Mg(2+) in the mM range in the cytosol for further development of structure-based anti-allergic drugs.
About this Structure
1V40 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase., Inoue T, Okano Y, Kado Y, Aritake K, Irikura D, Uodome N, Okazaki N, Kinugasa S, Shishitani H, Matsumura H, Kai Y, Urade Y, J Biochem. 2004 Mar;135(3):279-83. PMID:15113825
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