2RQ0

Solution Structure of Mouse Lipocalin-type Prostaglandin D Synthase Possessing the Intrinsic Disulfide Bond

Summary for 2RQ0

• Entry DOI: 10.2210/pdb2rq0/pdb
• NMR Information: BMRB: 11062
• Descriptor: Prostaglandin-H2 D-isomerase (1 entity in total)
• Functional Keywords: lipocalin, beta-barrel, cytoplasm, endoplasmic reticulum, fatty acid biosynthesis, glycoprotein, golgi apparatus, isomerase, lipid synthesis, membrane, nucleus, prostaglandin biosynthesis, pyrrolidone carboxylic acid, secreted, transport
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 18617.86

Authors

Miyamoto, Y.,Nishimura, S.,Inui, T. (deposition date: 2008-12-24, release date: 2009-12-15, Last modification date: 2024-10-30)

Primary citation

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., 2009

PubMed Abstract: 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.

PubMed: 19833210
DOI: 10.1016/j.jsb.2009.10.005

Experimental method

SOLUTION NMR