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Structural basis for bifunctional peptide recognition at human δ-opioid receptor.

Gustavo FenaltiNadia A ZatsepinCecilia BettiPatrick GiguereGye Won HanAndrii IshchenkoWei LiuKarel GuillemynHaitao ZhangDaniel JamesDingjie WangUwe WeierstallJohn C H SpenceSébastien BoutetMarc MesserschmidtGarth J WilliamsCornelius GatiOleksandr M YefanovThomas A WhiteDominik OberthuerMarkus MetzChun Hong YoonAnton BartyHenry N ChapmanShibom BasuJesse D CoeChelsie E ConradRaimund FrommePetra FrommeDirk TourwéPeter W SchillerBryan L RothSteven BalletVsevolod KatritchRaymond C StevensVadim Cherezov
Published in: Nature structural & molecular biology (2015)
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.
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