| Structural highlights
Function
PTGDS_HUMAN 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]
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 prostaglandin D synthase (L-PGDS) regulates synthesis of an important inflammatory and signaling mediator, prostaglandin D2 (PGD2). Here, we used structural, biophysical, and biochemical approaches to address the mechanistic aspects of substrate entry, catalysis, and product exit of this enzyme. Structure of human L-PGDS was solved in a complex with a substrate analog (SA) and in ligand-free form. Its catalytic Cys 65 thiol group was found in two different conformations, each making a distinct hydrogen bond network to neighboring residues. These help in elucidating the mechanism of the cysteine nucleophile activation. Electron density for ligand observed in the active site defined the substrate binding regions, but did not allow unambiguous fitting of the SA. To further understand ligand binding, we used NMR spectroscopy to map the binding sites and to show the dynamics of protein-substrate and protein-product interactions. A model for ligand binding at the catalytic site is proposed, showing a second binding site involved in ligand exit and entry. NMR chemical shift perturbations and NMR resonance line-width alterations (observed as changes of intensity in two-dimensional cross-peaks in [(1)H,(15)N]-transfer relaxation optimization spectroscopy) for residues at the Omega loop (A-B loop), E-F loop, and G-H loop besides the catalytic sites indicate involvement of these residues in ligand entry/egress.
Structural and dynamic insights into substrate binding and catalysis of human lipocalin prostaglandin D synthase.,Lim SM, Chen D, Teo H, Roos A, Jansson AE, Nyman T, Tresaugues L, Pervushin K, Nordlund P J Lipid Res. 2013 Jun;54(6):1630-43. doi: 10.1194/jlr.M035410. Epub 2013 Mar 22. PMID:23526831[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tokugawa Y, Kunishige I, Kubota Y, Shimoya K, Nobunaga T, Kimura T, Saji F, Murata Y, Eguchi N, Oda H, Urade Y, Hayaishi O. Lipocalin-type prostaglandin D synthase in human male reproductive organs and seminal plasma. Biol Reprod. 1998 Feb;58(2):600-7. PMID:9475419
- ↑ Zhou Y, Shaw N, Li Y, Zhao Y, Zhang R, Liu ZJ. Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules. FASEB J. 2010 Dec;24(12):4668-77. doi: 10.1096/fj.10-164863. Epub 2010 Jul 28. PMID:20667974 doi:10.1096/fj.10-164863
- ↑ Lim SM, Chen D, Teo H, Roos A, Jansson AE, Nyman T, Tresaugues L, Pervushin K, Nordlund P. Structural and dynamic insights into substrate binding and catalysis of human lipocalin prostaglandin D synthase. J Lipid Res. 2013 Jun;54(6):1630-43. doi: 10.1194/jlr.M035410. Epub 2013 Mar 22. PMID:23526831 doi:10.1194/jlr.M035410
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