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8hta

From Proteopedia

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Solution Structure of the C65A/C167A Mutant of Human Lipocalin-type Prostaglandin D Synthase

Structural highlights

8hta is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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) is a secretory lipid-transporter protein that was shown to bind a wide variety of hydrophobic ligands in vitro. Exploiting this function, we previously examined the feasibility of using L-PGDS as a novel delivery vehicle for poorly water-soluble drugs. However, the mechanism by which human L-PGDS binds to poorly water-soluble drugs is unclear. In this study, we determined the solution structure of human L-PGDS and investigated the mechanism of L-PGDS binding to 6-nitro-7-sulfamoyl-benzo[f]quinoxalin-2,3-dione (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor antagonist. NMR experiments showed that human L-PGDS has an eight-stranded antiparallel beta-barrel structure that forms a central cavity, a short 3(10) -helix and two alpha-helices. Titration with NBQX was monitored using (1) H-(15) N HSQC spectroscopy. At higher NBQX concentrations, some cross-peaks of the protein exhibited fast-exchanging shifts with a curvature, indicating at least two binding sites. These residues were located in the upper portion of the cavity. Singular value decomposition analysis revealed that human L-PGDS has two NBQX binding sites. Large chemical shift changes were observed in the H2-helix and A-, B-, C-, D-, H- and I-strands and H2-helix upon NBQX binding. Calorimetric experiments revealed that human L-PGDS binds two NBQX molecules with dissociation constants of 46.7 mum for primary binding and 185.0 mum for secondary binding. Molecular docking simulations indicated that these NBQX binding sites are located within the beta-barrel. These results provide new insights into the interaction between poorly water-soluble drugs and human L-PGDS as a drug carrier.

Structural and interaction analysis of human lipocalin-type prostaglandin D synthase with the poorly water-soluble drug NBQX.,Miyamoto Y, Nakatsuji M, Yoshida T, Ohkubo T, Inui T FEBS J. 2023 Apr 6. doi: 10.1111/febs.16791. PMID:37021622^[3]

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

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
↑ Miyamoto Y, Nakatsuji M, Yoshida T, Ohkubo T, Inui T. Structural and interaction analysis of human lipocalin-type prostaglandin D synthase with the poorly water-soluble drug NBQX. FEBS J. 2023 Apr 6. PMID:37021622 doi:10.1111/febs.16791

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8hta"

Categories: Homo sapiens | Large Structures | Inui T | Miyamoto Y

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8hta]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HTA FirstGlance]. <br>
-</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=8hta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hta OCA], [https://pdbe.org/8hta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hta RCSB], [https://www.ebi.ac.uk/pdbsum/8hta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hta ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=8hta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hta OCA], [https://pdbe.org/8hta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hta RCSB], [https://www.ebi.ac.uk/pdbsum/8hta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hta ProSAT]</span></td></tr>
 </table>
 == Function ==

8hta

From Proteopedia

Current revision

Solution Structure of the C65A/C167A Mutant of Human Lipocalin-type Prostaglandin D Synthase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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