Extreme C‐terminal element of SprA serine integrase is a potential component of the “molecular toggle switch” which controls the recombination and its directionality

2020 ◽  
Author(s):  
Kimihiro Abe ◽  
Takumi Takahashi ◽  
Tsutomu Sato
2021 ◽  
Vol 22 (7) ◽  
pp. 3671
Author(s):  
Magdalena Ulanowska ◽  
Beata Olas

Eugenol is a phenolic aromatic compound obtained mainly from clove oil. Due to its known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory and antioxidant properties, it has long been used in various areas, such as cosmetology, medicine, and pharmacology. However, high concentrations can be toxic. A dose of 2.5 mg/kg body weight is regarded as safe. This paper reviews the current state of knowledge regarding the activities and application of eugenol and its derivatives and recent research of these compounds. This review is based on information concerning eugenol characteristics and recent research from articles in PubMed. Eugenol remains of great interest to researchers, since its multidirectional action allows it to be a potential component of drugs and other products with therapeutic potential against a range of diseases.


2021 ◽  
Vol 7 (14) ◽  
pp. eabf1268
Author(s):  
Changxiu Qu ◽  
Chunyou Mao ◽  
Peng Xiao ◽  
Qingya Shen ◽  
Ya-Ni Zhong ◽  
...  

Selective modulation of the heterotrimeric G protein α S subunit–coupled prostaglandin E2 (PGE2) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo–electron microscopy structure of the EP2-Gs complex with its endogenous agonist PGE2 and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W6.48 “toggle switch” and coupling to Gs via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE2 signaling system.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 815 ◽  
Author(s):  
Egle Rebane-Klemm ◽  
Laura Truu ◽  
Leenu Reinsalu ◽  
Marju Puurand ◽  
Igor Shevchuk ◽  
...  

This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry. ADP-activated respiration rate (Vmax) and an apparent affinity of mitochondria to ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower Vmax values compared to wild-type; however, the Vmax value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated polyps had higher Vmax values and elevated MOM permeability as compared to the control. BRAF mutated CRC and polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and polyps. Assessment of the tumor mitochondrial ATP synthesis could be a potential component of patient risk stratification.


1995 ◽  
Vol 57 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Nashaat N. Boutros ◽  
Michael W. Torello ◽  
Brandy A. Barker ◽  
Patricia A. Tueting ◽  
Shu-Chieh Wu ◽  
...  

2014 ◽  
Vol 116 (5) ◽  
pp. 659-662 ◽  
Author(s):  
Olga Gawrys ◽  
Krzysztof Hubert Olszyński ◽  
Katarzyna Gawarecka ◽  
Ewa Swiezewska ◽  
Tadeusz Chojnacki ◽  
...  

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