Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Biased allosteric activation of ketone body receptor HCAR2 suppresses inflammation.
Journal, issue, pages	Mol Cell, Vol. 83, Issue 17, Page 3171-33187.e7, Year 2023
Publish date	Sep 7, 2023
Authors	Chang Zhao / Heli Wang / Ying Liu / Lin Cheng / Bo Wang / Xiaowen Tian / Hong Fu / Chao Wu / Ziyan Li / Chenglong Shen / Jingjing Yu / Shengyong Yang / Hongbo Hu / Ping Fu / Liang Ma / Chuanxin Wang / Wei Yan / Zhenhua Shao /
PubMed Abstract	Hydroxycarboxylic acid receptor 2 (HCAR2), modulated by endogenous ketone body β-hydroxybutyrate and exogenous niacin, is a promising therapeutic target for inflammation-related diseases. HCAR2 ...Hydroxycarboxylic acid receptor 2 (HCAR2), modulated by endogenous ketone body β-hydroxybutyrate and exogenous niacin, is a promising therapeutic target for inflammation-related diseases. HCAR2 mediates distinct pathophysiological events by activating G protein or β-arrestin effectors. Here, we characterize compound 9n as a G-biased allosteric modulator (BAM) of HCAR2 and exhibit anti-inflammatory efficacy in RAW264.7 macrophages via a specific HCAR2-G pathway. Furthermore, four structures of HCAR2-G complex bound to orthosteric agonists (niacin or monomethyl fumarate), compound 9n, and niacin together with compound 9n simultaneously reveal a common orthosteric site and a unique allosteric site. Combined with functional studies, we decipher the action framework of biased allosteric modulation of compound 9n on the orthosteric site. Moreover, co-administration of compound 9n with orthosteric agonists could enhance anti-inflammatory effects in the mouse model of colitis. Together, our study provides insight to understand the molecular pharmacology of the BAM and facilitates exploring the therapeutic potential of the BAM with orthosteric drugs.
External links	Mol Cell / PubMed:37597514
Methods	EM (single particle)
Resolution	2.78 - 3.5 Å
Structure data	36300 8jhy EMDB-36300, PDB-8jhy: Cryo-EM structure of compound 9n bound ketone body receptor HCAR2-Gi signaling complex Method: EM (single particle) / Resolution: 2.87 Å 36312 8jii EMDB-36312, PDB-8jii: Cryo-EM structure of compound 9n and niacin bound ketone body receptor HCAR2-Gi signaling complex Method: EM (single particle) / Resolution: 3.17 Å 36317 8jil EMDB-36317, PDB-8jil: Cryo-EM structure of niacin bound ketone body receptor HCAR2-Gi signaling complex Method: EM (single particle) / Resolution: 3.5 Å 36318 8jim EMDB-36318, PDB-8jim: Cryo-EM structure of MMF bound ketone body receptor HCAR2-Gi signaling complex Method: EM (single particle) / Resolution: 2.98 Å EMDB-36490: Cryo-EM map of human receptor R2 Method: EM (single particle) / Resolution: 3.21 Å EMDB-36491: Cryo-EM map of human Gi heterotrimer Method: EM (single particle) / Resolution: 2.78 Å EMDB-36492: Cryo-EM map of human receptor R2 Method: EM (single particle) / Resolution: 3.37 Å EMDB-36493: Cryo-EM map of human Gi heterotrimer Method: EM (single particle) / Resolution: 3.12 Å EMDB-36494: Cryo-EM map of human receptor R2 Method: EM (single particle) / Resolution: 3.24 Å EMDB-36495: Cryo-EM map of human Gi heterotrimer Method: EM (single particle) / Resolution: 2.95 Å EMDB-36496: Cryo-EM map of human receptor R2 Method: EM (single particle) / Resolution: 3.37 Å EMDB-36497: Cryo-EM map of human Gi heterotrimer Method: EM (single particle) / Resolution: 2.96 Å EMDB-36505: Cryo-EM map of human receptor R2 in complex with Gi protein Method: EM (single particle) / Resolution: 2.87 Å EMDB-36506: Cryo-EM map of human receptor R2 in complex with Gi protein Method: EM (single particle) / Resolution: 3.17 Å EMDB-36507: Cryo-EM map of human receptor R2 in complex with Gi protein Method: EM (single particle) / Resolution: 3.05 Å EMDB-36508: Cryo-EM map of human receptor R2 in complex with Gi protein Method: EM (single particle) / Resolution: 2.98 Å
Chemicals	ChemComp-IX8: 7-methyl-N-[(2R)-1-phenoxypropan-2-yl]-3-(4-propan-2-ylphenyl)pyrazolo[1,5-a]pyrimidine-6-carboxamide ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-NIO: NICOTINIC ACID / Niacin ChemComp-HOH: WATER / Water ChemComp-AW9: (2Z)-4-methoxy-4-oxobut-2-enoic acid
Source	homo sapiens (human) mus musculus (house mouse)
Keywords	MEMBRANE PROTEIN / Complex / Agonist