scholarly journals Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gaohua Yang ◽  
Sen Hong ◽  
Pengjie Yang ◽  
Yuwei Sun ◽  
Yong Wang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Crystal Structure Analysis ◽  
Polyphenolic Compounds ◽  
Personalized Nutrition ◽  
Biochemical Analyses ◽  
Microbial Consumption ◽  
Insight Into

AbstractGut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2–C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine.

scholarly journals Mechanism for autoinhibition and activation of the MORC3 ATPase

2019 ◽  
Vol 116 (13) ◽  
pp. 6111-6119 ◽  
Author(s):  
Yi Zhang ◽  
Brianna J. Klein ◽  
Khan L. Cox ◽  
Bianca Bertulat ◽  
Adam H. Tencer ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Activity ◽  
Molecular Basis ◽  
Catalytic Domain ◽  
Histone H3 ◽  
Protein Fold ◽  
Atpase Domain ◽  
Dna Binding Site ◽  
Dimeric Form ◽  
Biochemical Analyses

Microrchidia 3 (MORC3) is a human protein linked to autoimmune disorders, Down syndrome, and cancer. It is a member of a newly identified family of human ATPases with an uncharacterized mechanism of action. Here, we elucidate the molecular basis for inhibition and activation of MORC3. The crystal structure of the MORC3 region encompassing the ATPase and CW domains in complex with a nonhydrolyzable ATP analog demonstrates that the two domains are directly coupled. The extensive ATPase:CW interface stabilizes the protein fold but inhibits the catalytic activity of MORC3. Enzymatic, NMR, mutational, and biochemical analyses show that in the autoinhibited, off state, the CW domain sterically impedes binding of the ATPase domain to DNA, which in turn is required for the catalytic activity. MORC3 autoinhibition is released by disrupting the intramolecular ATPase:CW coupling through the competitive interaction of CW with histone H3 tail or by mutating the interfacial residues. Binding of CW to H3 leads to a marked rearrangement in the ATPase–CW cassette, which frees the DNA-binding site in active MORC3 (on state). We show that ATP-induced dimerization of the ATPase domain is strictly required for the catalytic activity and that the dimeric form of ATPase–CW might cooperatively bind to dsDNA. Together, our findings uncovered a mechanism underlying the fine-tuned regulation of the catalytic domain of MORC3 by the epigenetic reader, CW.

scholarly journals Goji Berries as a Potential Natural Antioxidant Medicine: An Insight into Their Molecular Mechanisms of Action

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zheng Feei Ma ◽  
Hongxia Zhang ◽  
Sue Siang Teh ◽  
Chee Woon Wang ◽  
Yutong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Complex Mixture ◽  
Mechanisms Of Action ◽  
Pharmacological Properties ◽  
Additive Effects ◽  
Herbal Tea ◽  
Herbal Products ◽  
Goji Berries ◽  
Insight Into

Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.

scholarly journals Crystal structure analysis of EstA fromArthrobactersp. Rue61a - an insight into catalytic promiscuity

FEBS Letters ◽  
2014 ◽  
Vol 588 (7) ◽  
pp. 1154-1160 ◽  
Author(s):  
Ulrike Gabriella Wagner ◽  
Frank DiMaio ◽  
Stephan Kolkenbrock ◽  
Susanne Fetzner
Keyword(s):  
Crystal Structure ◽  
Structure Analysis ◽  
Crystal Structure Analysis ◽  
Catalytic Promiscuity ◽  
Insight Into

scholarly journals Neuroprotective Potential of Silymarin against CNS Disorders: Insight into the Pathways and Molecular Mechanisms of Action

2013 ◽  
Vol 19 (11) ◽  
pp. 847-853 ◽  
Author(s):  
Anupom Borah ◽  
Rajib Paul ◽  
Sabanum Choudhury ◽  
Amarendranath Choudhury ◽  
Bornalee Bhuyan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Cns Disorders ◽  
Insight Into

Crystal Structure Analysis of Cu-Zr Alloys by Convergent Beam Diffraction

1981 ◽  
Vol 39 ◽  
pp. 354-355
Author(s):  
A. F. Marshall ◽  
J. W. Steeds ◽  
D. Bouchet ◽  
S. L. Shinde ◽  
R. G. Walmsley
Keyword(s):  
Crystal Structure ◽  
Point Group ◽  
Intermetallic Phase ◽  
Three Dimensional ◽  
Crystal Structure Analysis ◽  
Ion Milling ◽  
Composition And Structure ◽  
Unit Cells ◽  
Sputter Deposited ◽  
Convergent Beam

Convergent beam electron diffraction is a powerful technique for determining the crystal structure of a material in TEM. In this paper we have applied it to the study of the intermetallic phases in the Cu-rich end of the Cu-Zr system. These phases are highly ordered. Their composition and structure has been previously studied by microprobe and x-ray diffraction with sometimes conflicting results.The crystalline phases were obtained by annealing amorphous sputter-deposited Cu-Zr. Specimens were thinned for TEM by ion milling and observed in a Philips EM 400. Due to the large unit cells involved, a small convergence angle of diffraction was used; however, the three-dimensional lattice and symmetry information of convergent beam microdiffraction patterns is still present. The results are as follows:1) 21 at% Zr in Cu: annealed at 500°C for 5 hours. An intermetallic phase, Cu3.6Zr (21.7% Zr), space group P6/m has been proposed near this composition (2). The major phase of our annealed material was hexagonal with a point group determined as 6/m.

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