المؤلفون: Zhou, Yan, Zhang, Qiang, Xu, Feihu, Liu, Bo, Zhang, Bingqiang, Wang, Sanzhao, Ma, Xixiang, Chen, Long, Feng, Yuechong, Shi, Pan

المصدر: Proceedings of SPIE; April 2024, Vol. 13155 Issue: 1 p131550D-131550D-5, 1183956p

المؤلفون: Zhou, Yan, Zhang, Qiang, Xu, Feihu, Liu, Bo, Ma, Xixiang, Wang, Sanzhao, Shi, Pan, Chen, Long

المصدر: Proceedings of SPIE; April 2024, Vol. 13155 Issue: 1 p131550B-131550B-4, 1183955p

المؤلفون: Ling, Shenglong, Meng, Xianyu, Zhang, Yuan, Xia, Zhemin, Zhou, Yingxin, Yang, Fan, Shi, Pan, Shi, Chaowei, Tian, Changlin

المصدر: Cell Research; February 2024, Vol. 34 Issue: 2 p169-172, 4p

المؤلفون: Li, Ying-ge, Meng, Xian-yu, Yang, Xiru, Ling, Sheng-long, Shi, Pan, Tian, Chang-lin, Yang, Fan

المصدر: Acta Pharmacologica Sinica; 20240101, Issue: Preprints p1-9, 9p

مستخلص: Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing’s disease. Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2. Pasireotide is preferential binding to SSTR5 than octreotide, while octreotide is biased to SSTR2 than SSTR5. The lack of selectivity of both pasireotide and octreotide causes side effects, such as hyperglycemia, gastrointestinal disturbance, and abnormal glucose homeostasis. However, little is known about the binding and selectivity mechanisms of pasireotide and octreotide with SSTR5, limiting the development of subtype-selective SST analog drugs specifically targeting SSTR5. Here, we report two cryo-electron microscopy (cryo-EM) structures of SSTR5-Gi complexes activated by pasireotide and octreoitde at resolutions of 3.09 Å and 3.24 Å, respectively. In combination with structural analysis and functional experiments, our results reveal the molecular mechanisms of ligand recognition and receptor activation. We also demonstrate that pasireotide preferentially binds to SSTR5 through the interactions between Tyr(Bzl)/DTrp of pasireotide and SSTR5. Moreover, we find that the Q2.63, N6.55, F7.35and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.

المؤلفون: Zhao, Rui, Shi, Pan, Wei, Xiao-Xiong, Xia, Zhemin, Shi, Chaowei, Shi, Jing

المصدر: Organic Letters; September 2023, Vol. 25 Issue: 35 p6544-6548, 5p

مستخلص: We report an intermolecular native chemical ligation-assisted diaminodiacid strategy for the flexible construction of A11Cys–B11Cysdisulfide surrogates of H2 relaxin. The practicality of this strategy was evidenced by the synthesis of four new H2 relaxin analogs, among which H2-2a-B28Ileis found to exhibit improved potency, selectivity, and stability compared with native H2 relaxin.

المؤلفون: Liu, Jun-ping, Yin, Wei, Yang, Shi-pan, Zhao, Jiang-tai, Zeng, Wen-tao, Tang, Feng, He, Shi-jun, Li, Wei-ke

المصدر: China Geology; January 2023, Vol. 6 Issue: 1 p50-60, 11p

مستخلص: The Lomagundi-Jatuli Event (LJE) refers to the significant positive carbon isotope excursion in seawater constituents that occurred immediately after the increase in atmospheric oxygen content during the Paleoproterozoic (2.22–2.06 Ga). The δ13C values of 46 dolostone samples collected from the Paleoproterozoic Yongjingshao Formation varied in the range of 0.05 ‰–4.95 ‰ (V-PDB; maximum: 4.95‰) in this study, which may be related to the multicellular eukaryotes in the Liangshan Formation in the Yimen Group. They are much higher than the δ13C values of marine carbonates (−1.16‰ on average). The δ13C values of other formations in the Paleoproterozoic Yimen Group are negative. The notable positive carbon isotope anomalies of the Yongjingshao Formation indicate the response to the LJE at the southwestern margin of the Yangtze Block, which is reported for the first time. Furthermore, they are comparable to the δ13C values of carbonates in the Dashiling Formation of the Hutuo Group in the Wutaishan area in the North China Craton, the Wuzhiling Formation of the Songshan Group in the Xiong’ er area, Henan Province, and the Dashiqiao Formation of the Liaohe Group in the Guanmenshan area, Liaoning Province. Therefore, it can be further concluded that the LJE is a global event. This study reveals that LJE occurred in Central Yunnan at 2.15–2.10 Ga, lasting for about 50 Ma. The macro-columnar, bean-shaped, and microfilament fossils and reticular ultramicrofossils of multicellular eukaryotes in this period were discovered in the Liangshan Formation of the Yimen Group. They are the direct cause for the LJE and are also the oldest paleontological fossils ever found. The major events successively occurring in the early stage of the Earth include the Great Oxygenation Event (first occurrence), the global Superior-type banded iron formations (BIFs), the Huronian glaciation, the Great Oxygenation Event (second occurrence), the explosion of multicellular eukaryotes, the positive carbon isotope excursion, and the global anoxic and selenium-rich sedimentary event. The authors think that the North China Craton and the Yangtze Craton were possibly in different tectonic locations of the same continental block during the Proterozoic.

المؤلفون: Fang, Wei, Yang, Fan, Xu, Chanjuan, Ling, Shenglong, Lin, Li, Zhou, Yingxin, Sun, Wenjing, Wang, Xiaomei, Liu, Peng, Rondard, Philippe, Shi, Pan, Pin, Jean-Philippe, Tian, Changlin, Liu, Jianfeng

المصدر: Cell Research; July 2022, Vol. 32 Issue: 7 p695-698, 4p

المؤلفون: Su, Junhong, Chen, Lianghui, Chu, Junhao, Zhu, Shining, Yu, Qifeng, Shi, Pan, Wang, Sanzhao, Ren, Hongyu, Chen, Long, Zheng, Han

المصدر: Proceedings of SPIE; March 2022, Vol. 12169 Issue: 1 p12169BP-12169BP-7, 109529p

المؤلفون: Li, Longmei, Zhang, Jin, Sun, Wenjing, Gong, Weimin, Tian, Changlin, Shi, Pan, Shi, Chaowei

المصدر: Chinese Chemical Letters; February 2022, Vol. 33 Issue: 2 p747-750, 4p

مستخلص: Current resolved structures of GPCRs and G protein complexes provided important insights into G protein activation. However, the binding or dissociation of GPCRs with G protein is instantaneous and highly dynamic in the intracellular environment. The conformational dynamic of G protein still needs to be addressed. In this study, we applied 19F solution NMR spectroscopy to monitor the conformational changes of G protein upon interact with detergent mimicking membrane and receptor. Our results show that there are two states equilibria in the Gαin apo states. The interaction of Gαwith detergents will accelerate this conformational transformation and induce a state that tends to bind to GPCRs. Finally, the Gαproteins presented a fully activation state when they coupled to GPCRs.

المؤلفون: Yang, Fan, Zhang, Huanhuan, Meng, Xianyu, Li, Yingge, Zhou, Yingxin, Ling, Shenglong, Sun, Demeng, Lv, Pei, Liu, Lei, Shi, Pan, Tian, Changlin

المصدر: Cell Research; 20220101, Issue: Preprints p1-4, 4p