4RWA

Synchrotron structure of the human delta opioid receptor in complex with a bifunctional peptide (PSI community target)

Summary for 4RWA

• Entry DOI: 10.2210/pdb4rwa/pdb
• Related: 4EJ4 4N6H 4RWD
• Related PRD ID: PRD_001256
• Descriptor: Soluble cytochrome b562,Delta-type opioid receptor, bifunctional peptide, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• Functional Keywords: human opioid receptor, bifunctional peptide, gpcr signaling, gpcr network, membrane protein, psi-biology, structural genomics, gpcr, membrane, lipidic cubic phase, bril
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 92951.73

Authors

Fenalti, G.,Zatsepin, N.A.,Betti, C.,Giguere, P.,Han, G.W.,Ishchenko, A.,Liu, W.,Guillemyn, K.,Zhang, H.,James, D.,Wang, D.,Weierstall, U.,Spence, J.C.H.,Boutet, S.,Messerschmidt, M.,Williams, G.J.,Gati, C.,Yefanov, O.M.,White, T.A.,Oberthuer, D.,Metz, M.,Yoon, C.H.,Barty, A.,Chapman, H.N.,Basu, S.,Coe, J.,Conrad, C.E.,Fromme, R.,Fromme, P.,Tourwe, D.,Schiller, P.W.,Roth, B.L.,Ballet, S.,Katritch, V.,Stevens, R.C.,Cherezov, V.,GPCR Network (GPCR) (deposition date: 2014-12-01, release date: 2015-01-14, Last modification date: 2023-12-06)

Primary citation

Fenalti, G.,Zatsepin, N.A.,Betti, C.,Giguere, P.,Han, G.W.,Ishchenko, A.,Liu, W.,Guillemyn, K.,Zhang, H.,James, D.,Wang, D.,Weierstall, U.,Spence, J.C.,Boutet, S.,Messerschmidt, M.,Williams, G.J.,Gati, C.,Yefanov, O.M.,White, T.A.,Oberthuer, D.,Metz, M.,Yoon, C.H.,Barty, A.,Chapman, H.N.,Basu, S.,Coe, J.,Conrad, C.E.,Fromme, R.,Fromme, P.,Tourwe, D.,Schiller, P.W.,Roth, B.L.,Ballet, S.,Katritch, V.,Stevens, R.C.,Cherezov, V.
Structural basis for bifunctional peptide recognition at human delta-opioid receptor.
Nat.Struct.Mol.Biol., 22:265-268, 2015

PubMed Abstract: Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.

PubMed: 25686086
DOI: 10.1038/nsmb.2965

Experimental method

X-RAY DIFFRACTION (3.28 Å)