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

Gustavo Fenalti; Nadia A. Zatsepin; Cecilia Betti; Patrick Giguere; Gye Won Han; Andrii Ishchenko; Wei Liu; Karel Guillemyn; Haitao Zhang; Daniel James; Dingjie Wang; Uwe Weierstall; John C.H. Spence; Sébastien Boutet; Marc Messerschmidt; Garth J. Williams; Cornelius Gati; Oleksandr M. Yefanov; Thomas A. White; Dominik Oberthuer; Markus Metz; Chun Hong Yoon; Anton Barty; Henry N. Chapman; Shibom Basu; Jesse Coe; Chelsie E. Conrad; Raimund Fromme; Petra Fromme; Dirk Tourwé; Peter W. Schiller; Bryan L. Roth; Steven Ballet; Vsevolod Katritch; Raymond C. Stevens; Vadim Cherezov

doi:10.1038/nsmb.2965

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

Gustavo Fenalti
, Nadia A. Zatsepin
, Cecilia Betti
, Patrick Giguere
, Gye Won Han
, Andrii Ishchenko
, Wei Liu
, Karel Guillemyn
, Haitao Zhang
, Daniel James
, Dingjie Wang
, Uwe Weierstall
, John C.H. Spence
, Sébastien Boutet
, Marc Messerschmidt
, Garth J. Williams
, Cornelius Gati
, Oleksandr M. Yefanov
, Thomas A. White
, Dominik Oberthuer

Markus Metz, Chun Hong Yoon, Anton Barty, Henry N. Chapman, Shibom Basu, Jesse Coe, Chelsie E. Conrad, Raimund Fromme, Petra Fromme, Dirk Tourwé, Peter W. Schiller, Bryan L. Roth, Steven Ballet, Vsevolod Katritch, Raymond C. Stevens, Vadim Cherezov^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

165 Citations (Scopus)

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.

Original language	English
Pages (from-to)	265-268
Number of pages	4
Journal	Nature Structural and Molecular Biology
Volume	22
Issue number	3
DOIs	https://doi.org/10.1038/nsmb.2965
Publication status	Published - 6 Mar 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Nature America, Inc.

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10.1038/nsmb.2965

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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., ... Cherezov, V. (2015). Structural basis for bifunctional peptide recognition at human δ-opioid receptor. Nature Structural and Molecular Biology, 22(3), 265-268. https://doi.org/10.1038/nsmb.2965

@article{f3f5bac9711f43a99d93c4a0a395ca9a,

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 = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = mar,

day = "6",

doi = "10.1038/nsmb.2965",

language = "English",

volume = "22",

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journal = "Nature Structural and Molecular Biology",

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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, JCH, 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, Tourwé, D, Schiller, PW, Roth, BL, Ballet, S, Katritch, V, Stevens, RC & Cherezov, V 2015, 'Structural basis for bifunctional peptide recognition at human δ-opioid receptor', Nature Structural and Molecular Biology, vol. 22, no. 3, pp. 265-268. https://doi.org/10.1038/nsmb.2965

TY - JOUR

T1 - Structural basis for bifunctional peptide recognition at human δ-opioid receptor

AU - Fenalti, Gustavo

AU - Zatsepin, Nadia A.

AU - Betti, Cecilia

AU - Giguere, Patrick

AU - Han, Gye Won

AU - Ishchenko, Andrii

AU - Liu, Wei

AU - Guillemyn, Karel

AU - Zhang, Haitao

AU - James, Daniel

AU - Wang, Dingjie

AU - Weierstall, Uwe

AU - Spence, John C.H.

AU - Boutet, Sébastien

AU - Messerschmidt, Marc

AU - Williams, Garth J.

AU - Gati, Cornelius

AU - Yefanov, Oleksandr M.

AU - White, Thomas A.

AU - Oberthuer, Dominik

AU - Metz, Markus

AU - Yoon, Chun Hong

AU - Barty, Anton

AU - Chapman, Henry N.

AU - Basu, Shibom

AU - Coe, Jesse

AU - Conrad, Chelsie E.

AU - Fromme, Raimund

AU - Fromme, Petra

AU - Tourwé, Dirk

AU - Schiller, Peter W.

AU - Roth, Bryan L.

AU - Ballet, Steven

AU - Katritch, Vsevolod

AU - Stevens, Raymond C.

AU - Cherezov, Vadim

PY - 2015/3/6

Y1 - 2015/3/6

N2 - 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.

AB - 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.

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000350531000017

UR - https://openalex.org/W2126996939

U2 - 10.1038/nsmb.2965

DO - 10.1038/nsmb.2965

M3 - Journal Article

SN - 1545-9993

VL - 22

SP - 265

EP - 268

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 3

ER -

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

Abstract

Bibliographical note

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