PDBsum entry 4z34

Transport protein/inhibitor

PDB id: 4z34

Contents

Protein chain

385 a.a.

Ligands

ON7

1WV

PDB id:

4z34

Name:

Transport protein/inhibitor

Title:

Crystal structure of human lysophosphatidic acid receptor 1 in complex with ono9780307

Structure:

Lysophosphatidic acid receptor 1, soluble cytochrome b562. Chain: a. Fragment: unp residues 2-232. Unp residues 23-64. Unp residues 73- 127. Unp residues 248-326. Synonym: lpa-1,lysophosphatidic acid receptor edg-2,cytochrome b-562, cytochrome b-562,lpa-1,lysophosphatidic acid receptor edg-2. Engineered: yes. Mutation: yes

Source:

Homo sapiens, escherichia coli. Human. Organism_taxid: 9606, 562. Gene: lpar1, edg2, lpa1, cybc. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Expression_system_atcc_number: crl-1711.

Resolution:

3.00Å R-factor: 0.256 R-free: 0.281

Authors:

J.E.Chrencik,C.B.Roth,M.Terakado,H.Kurata,R.Omi,Y.Kihara, D.Warshaviak,S.Nakade,G.Asmar-Rovira,M.Mileni,H.Mizuno,M.T.Griffith, C.Rodgers,G.W.Han,J.Velasquez,J.Chun,R.C.Stevens,M.A.Hanson,Gpcr Network (Gpcr)

Key ref:

J.E.Chrencik et al. (2015). Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1. Cell, 161, 1633-1643. PubMed id: 26091040 DOI: 10.1016/j.cell.2015.06.002

Date:

30-Mar-15 Release date: 03-Jun-15

Protein chain

P0ABE7  (C562_ECOLX) -  Soluble cytochrome b562 from Escherichia coli

Seq: 128 a.a.

Struc: 385 a.a.*

Protein chain

Q92633  (LPAR1_HUMAN) -  Lysophosphatidic acid receptor 1 from Homo sapiens

Seq: 364 a.a.

Struc: 385 a.a.*

* PDB and UniProt seqs differ at 111 residue positions (black crosses)

DOI no: 10.1016/j.cell.2015.06.002

Cell 161:1633-1643 (2015)

PubMed id: 26091040

Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.

J.E.Chrencik, C.B.Roth, M.Terakado, H.Kurata, R.Omi, Y.Kihara, D.Warshaviak, S.Nakade, G.Asmar-Rovira, M.Mileni, H.Mizuno, M.T.Griffith, C.Rodgers, G.W.Han, J.Velasquez, J.Chun, R.C.Stevens, M.A.Hanson.

ABSTRACT

Lipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease.