| 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]
Publication Abstract from PubMed
Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the isomerization of the 9,11-endoperoxide group of PGH2 (prostaglandin H2) to produce PGD2 (prostaglandin D2) with 9-hydroxy and 11-keto groups. The product of the reaction, PGD2, is the precursor of several metabolites involved in many regulatory events. L-PGDS, the first member of the important lipocalin family to be recognized as an enzyme, is also able to bind and transport small hydrophobic molecules and was formerly known as beta-trace protein, the second most abundant protein in human cerebrospinal fluid. Previous structural work on the mouse and human proteins has focused on the identification of the amino acids responsible and the proposal of a mechanism for catalysis. In this paper, the X-ray structures of the apo and holo forms (bound to PEG) of the C65A mutant of human L-PGDS at 1.40 A resolution and of the double mutant C65A/K59A at 1.60 A resolution are reported. The apo forms of the double mutants C65A/W54F and C65A/W112F and the triple mutant C65A/W54F/W112F have also been studied. Mutation of the lysine residue does not seem to affect the binding of PEG to the ligand-binding cavity, and mutation of a single or both tryptophans appears to have the same effect on the position of these two aromatic residues at the entrance to the cavity. A solvent molecule has also been identified in an invariant position in the cavity of virtually all of the molecules present in the nine asymmetric units of the crystals that have been examined. Taken together, these observations indicate that the residues that have been mutated indeed appear to play a role in the entrance-exit process of the substrate and/or other ligands into/out of the binding cavity of the lipocalin.
High-resolution structures of mutants of residues that affect access to the ligand-binding cavity of human lipocalin-type prostaglandin D synthase.,Perduca M, Bovi M, Bertinelli M, Bertini E, Destefanis L, Carrizo ME, Capaldi S, Monaco HL Acta Crystallogr D Biol Crystallogr. 2014 Aug 1;70(Pt 8):2125-38. doi:, 10.1107/S1399004714012462. Epub 2014 Jul 25. PMID:25084332[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
- ↑ Perduca M, Bovi M, Bertinelli M, Bertini E, Destefanis L, Carrizo ME, Capaldi S, Monaco HL. High-resolution structures of mutants of residues that affect access to the ligand-binding cavity of human lipocalin-type prostaglandin D synthase. Acta Crystallogr D Biol Crystallogr. 2014 Aug 1;70(Pt 8):2125-38. doi:, 10.1107/S1399004714012462. Epub 2014 Jul 25. PMID:25084332 doi:http://dx.doi.org/10.1107/S1399004714012462
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