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3vi5

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Revision as of 18:47, 27 July 2022

Human hematopoietic prostaglandin D synthase inhibitor complex structures

Structural highlights

3vi5 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	1iyi, 1iyh, 1v40, 2cvd, 3vi7
Gene:	HPGDS, GSTS, PGDS, PTGDS2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HPGDS_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]

Publication Abstract from PubMed

In mast and Th2 cells, hematopoietic prostaglandin (PG) D synthase (H-PGDS) catalyses the isomerization of PGH(2) in the presence of glutathione (GSH) to produce the allergic and inflammatory mediator PGD(2). We determined the X-ray structures of human H-PGDS inhibitor complexes with 1-amino-4-{4-[4-chloro-6-(2-sulpho-phenylamino)-[1,3,5]triazin-2-ylmethyl]-3-sulp ho-phenylamino}-9,10-dioxo-9,10-dihydro-anthracene-2-sulphonic acid (Cibacron Blue) and 1-amino-4-(4-aminosulphonyl) phenyl-anthraquinone-2-sulphonic acid (APAS) at 2.0 A resolution. When complexed with H-PGDS, Cibacron Blue had an IC(50) value of 40 nM and APAS 2.1 muM. The Cibacron Blue molecule was stabilized by four hydrogen bonds and pi-pi stacking between the anthraquinone ring and Trp104, the ceiling of the active site H-PGDS pocket. Among the four hydrogen bonds, the Cibacron Blue terminal sulphonic group directly interacted with conserved residues Lys112 and Lys198, which recognize the PGH(2) substrate alpha-chain. In contrast, the APAS anthraquinone ring was inverted to interact with Trp104, while its benzenesulphonic group penetrated the GSH-bound region at the bottom of the active site. Due to the lack of extended aromatic rings, APAS could not directly hydrogen bond with the two conserved lysine residues, thus decreasing the total number of hydrogen bond from four to one. These factors may contribute to the 50-fold difference in the IC(50) values obtained for the two inhibitors.

Human hematopoietic prostaglandin D synthase inhibitor complex structures.,Kado Y, Aritake K, Uodome N, Okano Y, Okazaki N, Matsumura H, Urade Y, Inoue T J Biochem. 2012 Apr;151(4):447-55. Epub 2012 Mar 13. PMID:22418579^[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
↑ Kado Y, Aritake K, Uodome N, Okano Y, Okazaki N, Matsumura H, Urade Y, Inoue T. Human hematopoietic prostaglandin D synthase inhibitor complex structures. J Biochem. 2012 Apr;151(4):447-55. Epub 2012 Mar 13. PMID:22418579 doi:10.1093/jb/mvs024

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3vi5"

@@ Line 1: / Line 1: @@
 ==Human hematopoietic prostaglandin D synthase inhibitor complex structures==
-<StructureSection load='3vi5' size='340' side='right' caption='[[3vi5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3vi5' size='340' side='right'caption='[[3vi5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3vi5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VI5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VI5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3vi5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VI5 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=M4M:1-AMINO-9,10-DIOXO-4-[(4-SULFAMOYLPHENYL)AMINO]-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>M4M</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=M4M:1-AMINO-9,10-DIOXO-4-[(4-SULFAMOYLPHENYL)AMINO]-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>M4M</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1iyi|1iyi]], [[1iyh|1iyh]], [[1v40|1v40]], [[2cvd|2cvd]], [[3vi7|3vi7]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1iyi|1iyi]], [[1iyh|1iyh]], [[1v40|1v40]], [[2cvd|2cvd]], [[3vi7|3vi7]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HPGDS, GSTS, PGDS, PTGDS2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HPGDS, GSTS, PGDS, PTGDS2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3vi5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vi5 OCA], [http://pdbe.org/3vi5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vi5 RCSB], [http://www.ebi.ac.uk/pdbsum/3vi5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vi5 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vi5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vi5 OCA], [https://pdbe.org/3vi5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vi5 RCSB], [https://www.ebi.ac.uk/pdbsum/3vi5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vi5 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/HPGDS_HUMAN HPGDS_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>
+[[https://www.uniprot.org/uniprot/HPGDS_HUMAN HPGDS_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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[Glutathione S-transferase|Glutathione S-transferase]]
+*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Inoue, T]]
 [[Category: Kado, Y]]

3vi5

From Proteopedia

Revision as of 18:47, 27 July 2022

Human hematopoietic prostaglandin D synthase inhibitor complex structures

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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