| Structural highlights
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) acts as both a PGD(2) synthase and an extracellular transporter for small lipophilic molecules. From a series of biochemical studies, it has been found that L-PGDS has an ability to bind a variety of lipophilic ligands such as biliverdin, bilirubin and retinoids in vitro. Therefore, we considered that it is necessary to clarify the molecular structure of L-PGDS upon binding ligand in order to understand the physiological relevance of L-PGDS as a transporter protein. We investigated a molecular structure of L-PGDS/biliverdin complex by small-angle X-ray scattering (SAXS) and multi-dimensional NMR measurements, and characterized the binding mechanism in detail. SAXS measurements revealed that L-PGDS has a globular shape and becomes compact by 1.3A in radius of gyration on binding biliverdin. NMR experiments revealed that L-PGDS possessed an eight-stranded antiparallel beta-barrel forming a central cavity. Upon the titration with biliverdin, some cross-peaks for residues surrounding the cavity and EF-loop and H2-helix above the beta-barrel shifted, and the intensity of other cross-peaks decreased with signal broadenings in (1)H-(15)N heteronuclear single quantum coherence spectra. These results demonstrate that L-PGDS holds biliverdin within the beta-barrel, and the conformation of the loop regions above the beta-barrel changes upon binding biliverdin. Through such a conformational change, the whole molecule of L-PGDS becomes compact.
Structural analysis of lipocalin-type prostaglandin D synthase complexed with biliverdin by small-angle X-ray scattering and multi-dimensional NMR.,Miyamoto Y, Nishimura S, Inoue K, Shimamoto S, Yoshida T, Fukuhara A, Yamada M, Urade Y, Yagi N, Ohkubo T, Inui T J Struct Biol. 2010 Feb;169(2):209-18. Epub 2009 Oct 13. PMID:19833210[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ 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
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