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

被引：142

作者：

Fenalti, Gustavo ^{[1
]}

Zatsepin, Nadia A. ^{[2
]}

Betti, Cecilia ^{[3
,4
]}

Giguere, Patrick ^{[5
,6
,7
]}

Han, Gye Won ^{[1
]}

Ishchenko, Andrii ^{[1
]}

Liu, Wei ^{[1
]}

Guillemyn, Karel ^{[3
,4
]}

Zhang, Haitao ^{[1
]}

James, Daniel ^{[2
]}

Wang, Dingjie ^{[2
]}

Weierstall, Uwe ^{[2
]}

Spence, John C. H. ^{[2
]}

Boutet, Sebastien ^{[8
]}

Messerschmidt, Marc ^{[8
]}

Williams, Garth J. ^{[8
]}

Gati, Cornelius ^{[9
]}

Yefanov, Oleksandr M. ^{[9
]}

White, Thomas A. ^{[9
]}

Oberthuer, Dominik ^{[9
,10
]}

Metz, Markus ^{[9
,11
]}

Yoon, Chun Hong ^{[9
,12
]}

Barty, Anton ^{[9
]}

Chapman, Henry N. ^{[9
,11
]}

Basu, Shibom ^{[13
,14
]}

Coe, Jesse ^{[13
,14
]}

Conrad, Chelsie E. ^{[13
,14
]}

Fromme, Raimund ^{[13
,14
]}

Fromme, Petra ^{[13
,14
]}

Tourwe, Dirk ^{[3
,4
]}

Schiller, Peter W. ^{[15
]}

Roth, Bryan L. ^{[5
,6
,7
]}

Ballet, Steven ^{[3
,4
]}

Katritch, Vsevolod ^{[1
]}

Stevens, Raymond C. ^{[1
]}

Cherezov, Vadim ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[2] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA

[3] Vrije Univ Brussel, Dept Chem, Brussels, Belgium

[4] Vrije Univ Brussel, Dept Bioengn Sci, Brussels, Belgium

[5] Univ N Carolina, Chapel Hill Med Sch, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA

[6] Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, Chapel Hill, NC USA

[7] Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC USA

[8] SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA USA

[9] Deutsch Elektronen Synchrotron DESY, Ctr Free Elect Laser Sci, Hamburg, Germany

[10] Univ Hamburg, Inst Biochem & Mol Biol, Hamburg, Germany

[11] Univ Hamburg, Dept Phys, Hamburg, Germany

[12] European Xray Free Electron Laser Facil XFEL GmbH, Hamburg, Germany

[13] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA

[14] Arizona State Univ, Biodesign Inst, Ctr Appl Struct Discovery, Tempe, AZ USA

[15] Clin Res Inst Montreal, Lab Chem Biol & Peptide Res, Montreal, PQ H2W 1R7, Canada

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2015年 / 22卷 / 03期

基金：

美国国家卫生研究院; 加拿大健康研究院; 美国国家科学基金会;

关键词：

SERIAL FEMTOSECOND CRYSTALLOGRAPHY; MU AGONIST/DELTA ANTAGONIST; POTENT; TOLERANCE; DEPENDENCE; MORPHINE; BOND; DMT;

D O I：

10.1038/nsmb.2965

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bifunctional 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.

引用

页码：265 / 268

页数：4

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