@article{a7bf84880c264a6292bba42cf991c8b0,
title = "Structural basis for bifunctional peptide recognition at human δ-opioid receptor",
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-NH 2 (DIPP-NH 2) 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.",
author = "Gustavo Fenalti and Zatsepin, {Nadia A.} and Cecilia Betti and Patrick Giguere and Han, {Gye Won} and Andrii Ishchenko and Wei Liu and Karel Guillemyn and Haitao Zhang and Daniel James and Dingjie Wang and Uwe Weierstall and Spence, {John C.H.} and S{\'e}bastien Boutet and Marc Messerschmidt and Williams, {Garth J.} and Cornelius Gati and Yefanov, {Oleksandr M.} and White, {Thomas A.} and Dominik Oberthuer and Markus Metz and Yoon, {Chun Hong} and Anton Barty and Chapman, {Henry N.} and Shibom Basu and Jesse Coe and Conrad, {Chelsie E.} and Raimund Fromme and Petra Fromme and Dirk Tourw{\'e} and Schiller, {Peter W.} and Roth, {Bryan L.} and Steven Ballet and Vsevolod Katritch and Stevens, {Raymond C.} and Vadim Cherezov",
note = "Funding Information: This work was supported by US National Institutes of Health (NIH), National Institute of General Medical Sciences grants U54 GM094618 (R.C.S., V.C. and V.K.), R01 GM108635 (V.C.), U54 GM094599 (P.F.), R01 GM095583 (P.F.) and P41 GM103393 (S. Boutet); US National Institute of Drug Abuse grants P01 DA035764 (V.C., V.K., B.L.R. and R.C.S.) and R01 DA017204 (B.L.R.); the US National Institute of Mental Health Psychoactive Drug Screening Program (P.G. and B.L.R.); the Michael Hooker Chair for Protein Therapeutics and Translational Proteomics to B.L.R.; and US National Science Foundation Science and Technology Center award 1231306 (J.C.H.S., P.F. and U.W.). Parts of this work were supported Funding Information: by the Helmholtz Association, the German Research Foundation (DFG) Cluster of Excellence {\textquoteleft}Center for Ultrafast Imaging{\textquoteright} and the German Federal Ministry of Education and Research (BMBF) projects FKZ 05K12CH1 (H.N.C., A.B., C.G., O.M.Y., T.A.W., D.O. and M. Metz) and 05K2012 (D.O. and H.N.C.). C.G. thanks the PIER Helmholtz Graduate School and the Helmholtz Association for financial support. M. Metz. acknowledges support from the Marie Curie Initial Training Network NanoMem (grant no. 317079). C.B., S. Ballet, D.T. and P.W.S. were supported by a collaboration convention between the Minist{\`e}re du D{\'e}veloppement Economique, de l{\textquoteright}Innovation et de l{\textquoteright}Exportation du Qu{\'e}bec (PSR-SIIRI-417) and the Research Foundation–Flanders (FWO Vlaanderen, grant FWOAL570) and by grants to P.W.S. from the Canadian Institutes of Health Research (CIHR) (MOP-89716) and the NIH (DA-004443). We thank J. Velasquez, T. Trinh, M. Chu and A. Walker. Parts of this research were carried out at the Linac Coherent Light Source (LCLS), a US National User Facility operated by Stanford University on behalf of the US Department of Energy, Office of Basic Energy Sciences and at the GM/CA CAT, beamline 23ID-B, Advanced Photon Source, which is supported by the US National Cancer Institute grant Y1-CO-1020 and the US National Institute of General Medical Sciences grant Y1-GM-1104. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",
year = "2015",
month = mar,
day = "6",
doi = "10.1038/nsmb.2965",
language = "English",
volume = "22",
pages = "265--268",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "3",
}