3ee2

From Proteopedia

(Difference between revisions)

Revision as of 15:20, 25 December 2014

Structure of human prostaglandin D-synthase (hGSTS1-1) in complex with nocodazole

Structural highlights

3ee2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2cvd, 1iyh, 1iyi, 1v40, 1pd2
Gene:	PGDS (Homo sapiens)
Activity:	Prostaglandin-D synthase, with EC number 5.3.99.2
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PTGD2_HUMAN] Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Prostaglandin D(2) synthesised by the hematopoietic prostaglandin D(2) synthase has a pro-inflammatory effect in allergic asthma, regulating many hallmark characteristics of the disease. Here we describe identification of hematopoietic prostaglandin D(2) synthase inhibitors including cibacron blue, bromosulfophthalein and ethacrynic acid. Expansion around the drug-like ethacrynic acid identified a novel inhibitor, nocodazole, and a fragment representing its aromatic core. Nocodazole binding was further characterised by docking calculations in combination with conformational strain analysis. The benzyl thiophene core was predicted to be buried in the active site, binding in the putative prostaglandin binding site, and a likely hydrogen bond donor site identified. X-ray crystallographic studies supported the predicted binding mode.

Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase.,Weber JE, Oakley AJ, Christ AN, Clark AG, Hayes JD, Hall R, Hume DA, Board PG, Smythe ML, Flanagan JU Eur J Med Chem. 2010 Feb;45(2):447-54. Epub 2009 Oct 23. PMID:19939518^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kanaoka Y, Fujimori K, Kikuno R, Sakaguchi Y, Urade Y, Hayaishi O. Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase. Eur J Biochem. 2000 Jun;267(11):3315-22. PMID:10824118
↑ Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, Meyer DJ, Murphy GJ, Smith SA, Hayes JD. Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochem J. 2001 Nov 1;359(Pt 3):507-16. PMID:11672424
↑ Suzuki T, Watanabe K, Kanaoka Y, Sato T, Hayaishi O. Induction of hematopoietic prostaglandin D synthase in human megakaryocytic cells by phorbol ester. Biochem Biophys Res Commun. 1997 Dec 18;241(2):288-93. PMID:9425264 doi:http://dx.doi.org/10.1006/bbrc.1997.7803
↑ Mahmud I, Ueda N, Yamaguchi H, Yamashita R, Yamamoto S, Kanaoka Y, Urade Y, Hayaishi O. Prostaglandin D synthase in human megakaryoblastic cells. J Biol Chem. 1997 Nov 7;272(45):28263-6. PMID:9353279
↑ Inoue T, Irikura D, Okazaki N, Kinugasa S, Matsumura H, Uodome N, Yamamoto M, Kumasaka T, Miyano M, Kai Y, Urade Y. Mechanism of metal activation of human hematopoietic prostaglandin D synthase. Nat Struct Biol. 2003 Apr;10(4):291-6. PMID:12627223 doi:10.1038/nsb907
↑ Inoue T, Okano Y, Kado Y, Aritake K, Irikura D, Uodome N, Okazaki N, Kinugasa S, Shishitani H, Matsumura H, Kai Y, Urade Y. First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase. J Biochem. 2004 Mar;135(3):279-83. PMID:15113825
↑ Aritake K, Kado Y, Inoue T, Miyano M, Urade Y. Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase. J Biol Chem. 2006 Jun 2;281(22):15277-86. Epub 2006 Mar 17. PMID:16547010 doi:10.1074/jbc.M506431200
↑ Weber JE, Oakley AJ, Christ AN, Clark AG, Hayes JD, Hall R, Hume DA, Board PG, Smythe ML, Flanagan JU. Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase. Eur J Med Chem. 2010 Feb;45(2):447-54. Epub 2009 Oct 23. PMID:19939518 doi:10.1016/j.ejmech.2009.10.025
↑ Weber JE, Oakley AJ, Christ AN, Clark AG, Hayes JD, Hall R, Hume DA, Board PG, Smythe ML, Flanagan JU. Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase. Eur J Med Chem. 2010 Feb;45(2):447-54. Epub 2009 Oct 23. PMID:19939518 doi:10.1016/j.ejmech.2009.10.025

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ee2"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3ee2]] is a 2 chain structure with 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=3EE2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EE2 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NZO:NOCODAZOLE'>NZO</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NZO:NOCODAZOLE'>NZO</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cvd|2cvd]], [[1iyh|1iyh]], [[1iyi|1iyi]], [[1v40|1v40]], [[1pd2|1pd2]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cvd|2cvd]], [[1iyh|1iyh]], [[1iyi|1iyi]], [[1v40|1v40]], [[1pd2|1pd2]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGDS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGDS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ee2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ee2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ee2 RCSB], [http://www.ebi.ac.uk/pdbsum/3ee2 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ee2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ee2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ee2 RCSB], [http://www.ebi.ac.uk/pdbsum/3ee2 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PTGD2_HUMAN PTGD2_HUMAN]] Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide.<ref>PMID:10824118</ref> <ref>PMID:11672424</ref> <ref>PMID:9425264</ref> <ref>PMID:9353279</ref> <ref>PMID:12627223</ref> <ref>PMID:15113825</ref> <ref>PMID:16547010</ref> <ref>PMID:19939518</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 32: @@
 ==See Also==
 *[[Glutathione S-transferase|Glutathione S-transferase]]
-*[[Prostaglandin D synthase|Prostaglandin D synthase]]
 == References ==
 <references/>
@@ Line 37: / Line 38: @@
 [[Category: Homo sapiens]]
 [[Category: Prostaglandin-D synthase]]
-[[Category: Oakley, A J.]]
+[[Category: Oakley, A J]]
 [[Category: Fatty acid biosynthesis]]
 [[Category: Glutathione transferase sigma]]

3ee2

From Proteopedia

Revision as of 15:20, 25 December 2014

Structure of human prostaglandin D-synthase (hGSTS1-1) in complex with nocodazole

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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