4rwd
XFEL structure of the human delta opioid receptor in complex with a bifunctional peptideXFEL structure of the human delta opioid receptor in complex with a bifunctional peptide
Structural highlights
FunctionC562_ECOLX Electron-transport protein of unknown function.OPRD_HUMAN G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.[1] [2] [3] Publication Abstract from PubMedBifunctional mu- and delta-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human delta-OR bound to the bifunctional delta-OR antagonist and mu-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. Structural basis for bifunctional peptide recognition at human delta-opioid receptor.,Fenalti G, Zatsepin NA, Betti C, Giguere P, Han GW, Ishchenko A, Liu W, Guillemyn K, Zhang H, James D, Wang D, Weierstall U, Spence JC, Boutet S, Messerschmidt M, Williams GJ, Gati C, Yefanov OM, White TA, Oberthuer D, Metz M, Yoon CH, Barty A, Chapman HN, Basu S, Coe J, Conrad CE, Fromme R, Fromme P, Tourwe D, Schiller PW, Roth BL, Ballet S, Katritch V, Stevens RC, Cherezov V Nat Struct Mol Biol. 2015 Mar;22(3):265-8. doi: 10.1038/nsmb.2965. Epub 2015 Feb , 16. PMID:25686086[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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OCA- Escherichia coli
- Homo sapiens
- Large Structures
- Synthetic construct
- Ballet S
- Barty A
- Basu S
- Betti C
- Boutet S
- Chapman HN
- Cherezov V
- Coe J
- Conrad CE
- Fenalti G
- Fromme P
- Fromme R
- Gati C
- Giguere P
- Guillemyn K
- Han GW
- Ishchenko A
- James D
- Katritch V
- Liu W
- Messerschmidt M
- Metz M
- Oberthuer D
- Roth BL
- Schiller PW
- Spence JCH
- Stevens RC
- Tourwe D
- Wang D
- Weierstall U
- White TA
- Williams GJ
- Yefanov OM
- Yoon CH
- Zatsepin NA
- Zhang H