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2czt

From Proteopedia

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lipocalin-type prostaglandin D synthase

Structural highlights

2czt is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

PTGDS_MOUSE Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophopic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system.^[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

Lipocalin type prostaglandin D synthase (L-PGDS) is a multifunctional protein acting as a somnogen (PGD2)-producing enzyme, an extracellular transporter of various lipophilic ligands, and an amyloid-beta chaperone in human cerebrospinal fluid. In this study, we determined the crystal structures of two different conformers of mouse L-PGDS, one with an open cavity of the beta-barrel and the other with a closed cavity due to the movement of the flexible E-F loop. The upper compartment of the central large cavity contains the catalytically essential Cys65 residue and its network of hydrogen bonds with the polar residues Ser45, Thr67, and Ser81, whereas the lower compartment is composed of hydrophobic amino acid residues that are highly conserved among other lipocalins. SH titration analysis combined with site-directed mutagenesis revealed that the Cys65 residue is activated by its interaction with Ser45 and Thr67 and that the S45A/T67A/S81A mutant showed less than 10% of the L-PGDS activity. The conformational change between the open and closed states of the cavity indicates that the mobile calyx contributes to the multiligand binding ability of L-PGDS.

Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase.,Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M, Miyano M, Urade Y, Hayaishi O J Biol Chem. 2009 Aug 14;284(33):22344-52. Epub 2009 Jun 22. PMID:19546224^[9]

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

References

↑ Hoffmann A, Bachner D, Betat N, Lauber J, Gross G. Developmental expression of murine Beta-trace in embryos and adult animals suggests a function in maturation and maintenance of blood-tissue barriers. Dev Dyn. 1996 Nov;207(3):332-43. PMID:8922532 doi:<332::AID-AJA10>3.0.CO;2-6 http://dx.doi.org/10.1002/(SICI)1097-0177(199611)207:3<332::AID-AJA10>3.0.CO;2-6
↑ Eguchi N, Minami T, Shirafuji N, Kanaoka Y, Tanaka T, Nagata A, Yoshida N, Urade Y, Ito S, Hayaishi O. Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):726-30. PMID:9892701
↑ Pinzar E, Kanaoka Y, Inui T, Eguchi N, Urade Y, Hayaishi O. Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4903-7. PMID:10781097 doi:http://dx.doi.org/10.1073/pnas.090093997
↑ Fujitani Y, Kanaoka Y, Aritake K, Uodome N, Okazaki-Hatake K, Urade Y. Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice. J Immunol. 2002 Jan 1;168(1):443-9. PMID:11751991
↑ Taniike M, Mohri I, Eguchi N, Beuckmann CT, Suzuki K, Urade Y. Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model. J Neurosci. 2002 Jun 15;22(12):4885-96. PMID:12077186
↑ Shimamoto S, Yoshida T, Inui T, Gohda K, Kobayashi Y, Fujimori K, Tsurumura T, Aritake K, Urade Y, Ohkubo T. NMR solution structure of lipocalin-type prostaglandin D synthase: evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the central cavity. J Biol Chem. 2007 Oct 26;282(43):31373-9. Epub 2007 Aug 22. PMID:17715133 doi:10.1074/jbc.M700123200
↑ Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M, Miyano M, Urade Y, Hayaishi O. Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase. J Biol Chem. 2009 Aug 14;284(33):22344-52. Epub 2009 Jun 22. PMID:19546224 doi:10.1074/jbc.M109.018341
↑ Miyamoto Y, Nishimura S, Inoue K, Shimamoto S, Yoshida T, Fukuhara A, Yamada M, Urade Y, Yagi N, Ohkubo T, Inui T. Structural analysis of lipocalin-type prostaglandin D synthase complexed with biliverdin by small-angle X-ray scattering and multi-dimensional NMR. J Struct Biol. 2010 Feb;169(2):209-18. Epub 2009 Oct 13. PMID:19833210 doi:10.1016/j.jsb.2009.10.005
↑ Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M, Miyano M, Urade Y, Hayaishi O. Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase. J Biol Chem. 2009 Aug 14;284(33):22344-52. Epub 2009 Jun 22. PMID:19546224 doi:10.1074/jbc.M109.018341

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/2czt"

@@ Line 1: / Line 1: @@
 ==lipocalin-type prostaglandin D synthase==
-<StructureSection load='2czt' size='340' side='right' caption='[[2czt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='2czt' size='340' side='right'caption='[[2czt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2czt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CZT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CZT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2czt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CZT FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2czu|2czu]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2czt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2czt OCA], [https://pdbe.org/2czt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2czt RCSB], [https://www.ebi.ac.uk/pdbsum/2czt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2czt ProSAT], [https://www.topsan.org/Proteins/RSGI/2czt TOPSAN]</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=2czt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2czt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2czt RCSB], [http://www.ebi.ac.uk/pdbsum/2czt PDBsum], [http://www.topsan.org/Proteins/RSGI/2czt TOPSAN]</span></td></tr>
+</table>
-<table>
+== Function ==
+[https://www.uniprot.org/uniprot/PTGDS_MOUSE PTGDS_MOUSE] Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophopic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system.<ref>PMID:8922532</ref> <ref>PMID:9892701</ref> <ref>PMID:10781097</ref> <ref>PMID:11751991</ref> <ref>PMID:12077186</ref> <ref>PMID:17715133</ref> <ref>PMID:19546224</ref> <ref>PMID:19833210</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cz/2czt_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cz/2czt_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2czt ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2czt" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 32: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Prostaglandin-D synthase]]
+[[Category: Ago H]]
-[[Category: Ago, H.]]
+[[Category: Aritake K]]
-[[Category: Aritake, K.]]
+[[Category: Hayaishi O]]
-[[Category: Hayaishi, O.]]
+[[Category: Inoue T]]
-[[Category: Inoue, T.]]
+[[Category: Irikura D]]
-[[Category: Irikura, D.]]
+[[Category: Kumasaka T]]
-[[Category: Kumasaka, T.]]
+[[Category: Miyano M]]
-[[Category: Miyano, M.]]
+[[Category: Urade Y]]
-[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
+[[Category: Yamamoto M]]
-[[Category: Urade, Y.]]
-[[Category: Yamamoto, M.]]
-[[Category: C2221 native]]
-[[Category: Isomerase]]
-[[Category: Lipocalin]]
-[[Category: Riken structural genomics/proteomics initiative]]
-[[Category: Rsgi]]
-[[Category: Structural genomic]]

2czt

From Proteopedia

Current revision

lipocalin-type prostaglandin D synthase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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