Abstract

Project 1 is responsible for achieving the Center‟
s Aim 1 goals;the immediate goal of Aim 1 studies is the structure solution of GPCRs and their co-crystals with ligands. The long range goal is to develop a better understanding of the structure-function relationship in GPCRs. Ultimately enough structures will be determined to provide a fine sampling of the various GPCR sequence families and, thus, enable reliable modeling and predictive docking studies of other close family members. Structures of receptors in complex with different ligands will be essential for developing a better understanding of their binding properties. Ultimately, this newly acquired knowledge can then be used to validate and to generate hypothesis regarding GPCRs mechanisms of action (e.g., in signal processing pathways). These new structures will have an enormous impact on furthering our understanding of a number of diseases and most probably will help accelerate success rates in drug discovery and therapeutics development studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM094618-04
Application #
8501564
Study Section
Special Emphasis Panel (ZGM1-CBB-3)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$640,546
Indirect Cost
$278,158

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Eddy, Matthew T; Gao, Zhan-Guo; Mannes, Philip et al. (2018) Extrinsic Tryptophans as NMR Probes of Allosteric Coupling in Membrane Proteins: Application to the A2A Adenosine Receptor. J Am Chem Soc 140:8228-8235
Eddy, Matthew T; Lee, Ming-Yue; Gao, Zhan-Guo et al. (2018) Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine Receptor. Cell 172:68-80.e12
Peng, Yao; McCorvy, John D; Harpsøe, Kasper et al. (2018) 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology. Cell 172:719-730.e14
Seidel, Lisa; Zarzycka, Barbara; Zaidi, Saheem A et al. (2017) Structural insight into the activation of a class B G-protein-coupled receptor by peptide hormones in live human cells. Elife 6:
Zhang, Haitao; Han, Gye Won; Batyuk, Alexander et al. (2017) Structural basis for selectivity and diversity in angiotensin II receptors. Nature 544:327-332
Ishchenko, Andrii; Cherezov, Vadim; Liu, Wei (2016) Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography. J Vis Exp :
Yang, Dehua; de Graaf, Chris; Yang, Linlin et al. (2016) Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R). J Biol Chem 291:12991-3004
Zhu, Lan; Weierstall, Uwe; Cherezov, Vadim et al. (2016) Serial Femtosecond Crystallography of Membrane Proteins. Adv Exp Med Biol 922:151-160
Leach, Katie; Gregory, Karen J; Kufareva, Irina et al. (2016) Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res 26:574-92
White, Thomas A; Barty, Anton; Liu, Wei et al. (2016) Serial femtosecond crystallography datasets from G protein-coupled receptors. Sci Data 3:160057

Showing the most recent 10 out of 115 publications