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- A conserved cation binding site in the DNA binding domain of forkhead box transcription factors regulates DNA binding by FOXP2. [Journal Article]
- ABArch Biochem Biophys 2018 Sep 15
- FOXP2 is a transcriptional repressor involved in development of the human brain and is the first gene product to be linked to the evolution of human speech. FOXP2 belongs to the FOX superfamily of pr...
FOXP2 is a transcriptional repressor involved in development of the human brain and is the first gene product to be linked to the evolution of human speech. FOXP2 belongs to the FOX superfamily of proteins that share a common winged helix DNA binding domain - the forkhead domain. A divalent cation (Mg2+ or Ca2+) has been identified bound to a group of highly conserved residues in a number of FOX forkhead domain crystal structures. This work aims to investigate the role of the conserved divalent cation binding site by studying both the structure and DNA-binding function of the FOXP2 forkhead domain when in the presence and absence of either cation (Mg2+or Ca2+). The presence of the cations does not significantly alter the structure of the apo-FOXP2 forkhead domain. However, when in the presence of a cognate oligonucleotide sequence, differences are observed upon addition of divalent cation. These differences occur both in the structure and in the thermodynamic DNA binding signature of the FOXP2 forkhead domain. The incorporation of molecular dynamics simulations together with the experimental data provides us with sufficient insight so as to propose a possible role for divalent cations in the regulation of DNA binding to FOX transcription factors.
- Cardiovascular Risk in Xavante Indigenous Population. [Journal Article]
- ABArq Bras Cardiol 2018; 110(6):542-550
- CONCLUSIONS: The Xavante have a high cardiovascular risk according to several indicators evaluated. The present analysis of cardiovascular risk factors provides support for the development of preventive measures and early treatment, in attempt to minimize the impact of cardiovascular diseases on this population.
- Structural basis of the arbitrium peptide-AimR communication system in the phage lysis-lysogeny decision. [Journal Article]
- NMNat Microbiol 2018 Sep 17
- A bacteriophage can replicate and release virions from a host cell in the lytic cycle or switch to a lysogenic process in which the phage integrates itself into the host genome as a prophage. In Baci...
A bacteriophage can replicate and release virions from a host cell in the lytic cycle or switch to a lysogenic process in which the phage integrates itself into the host genome as a prophage. In Bacillus cells, some types of phages employ the arbitrium communication system, which contains an arbitrium hexapeptide, the cellular receptor AimR and the lysogenic negative regulator AimX. This system controls the decision between the lytic and lysogenic cycles. However, both the mechanism of molecular recognition between the arbitrium peptide and AimR and how downstream gene expression is regulated remain unknown. Here, we report crystal structures for AimR from the SPbeta phage in the apo form and the arbitrium peptide-bound form at 2.20 Å and 1.92 Å, respectively. With or without the peptide, AimR dimerizes through the C-terminal capping helix. AimR assembles a superhelical fold and accommodates the peptide encircled by its tetratricopeptide repeats, which is reminiscent of RRNPP family members from the quorum-sensing system. In the absence of the arbitrium peptide, AimR targets the upstream sequence of the aimX gene; its DNA binding activity is prevented following peptide binding. In summary, our findings provide a structural basis for peptide recognition in the phage lysis-lysogeny decision communication system.
- Identification, functional characterization, and crystal structure determination of bacterial levoglucosan dehydrogenase. [Journal Article]
- JBJ Biol Chem 2018 Sep 17
- Levoglucosan is the 1,6-anhydrosugar of D-glucose formed by pyrolysis of glucans and is found in the environment and industrial waste. Two types of microbial levoglucosan metabolic pathways are known...
Levoglucosan is the 1,6-anhydrosugar of D-glucose formed by pyrolysis of glucans and is found in the environment and industrial waste. Two types of microbial levoglucosan metabolic pathways are known. Although the eukaryotic pathway involving levoglucosan kinase has been well studied, the bacterial pathway involving levoglucosan dehydrogenase (LGDH) has not been well investigated. Here, we identified and cloned the lgdh gene from the bacterium Pseudarthrobacter phenanthrenivorans and characterized the recombinant protein. The enzyme exhibited high substrate specificity toward levoglucosan and NAD+ for the oxidative reaction and was confirmed to be LGDH. LGDH also showed weak activities (~4%) toward L-sorbose and 1,5-anhydro-D-glucitol. The reverse (reductive) reaction using 3-keto levoglucosan and NADH exhibited significantly lower Km and higher kcat values than those of the forward reaction. The crystal structures of LGDH in the apo and complex forms with NADH, NADH + levoglucosan, and NADH + L-sorbose revealed that LGDH has a typical fold of Gfo/Idh/MocA family proteins, similar to those of scyllo-inositol dehydrogenase, aldose-aldose oxidoreductase, 1,5-anhydro-D-fructose reductase, and glucose-fructose oxidoreductase. The crystal structures also disclosed that the active site of LGDH is distinct from those of these enzymes. The LGDH active site extensively recognized the levoglucosan molecule with six hydrogen bonds, and the C3 atom of levoglucosan was closely located to the C4 atom of NADH nicotinamide. Our study is the first molecular characterization of LGDH, providing evidence for C3-specific oxidation, and representing a starting point for future biotechnological use of LGDH and levoglucosan-metabolizing bacteria.
- Adiposity mediates the association between whole grain consumption, glucose homeostasis and insulin resistance: findings from the US NHANES. [Journal Article]
- LHLipids Health Dis 2018 Sep 17; 17(1):219
- CONCLUSIONS: Our findings provide insights into the favourable impact of WG consumption on IR and inflammation, which may be affected by both central and visceral adiposity, i.e. the link between WG with IR and inflammation is more mediated in overweight/obese compared with lean individuals.
- Safety and efficacy of Melissa officinalis (lemon balm) on ApoA-I, Apo B, lipid ratio and ICAM-1 in type 2 diabetes patients: A randomized, double-blinded clinical trial. [Journal Article]
- CTComplement Ther Med 2018; 40:83-88
- CONCLUSIONS: M. officinalis is safe and effective in improvement of Apo A-I, Apo B/Apo A-I, and lipids ratios as key factors promoting cardiovascular disease (CVD) in type II diabetic patients.
- Effect of sumac (Rhus Coriaria) on blood lipids: A systematic review and meta-analysis. [Review]
- CTComplement Ther Med 2018; 40:8-12
- Cardiovascular diseases (CVD) are the prominent cause of mortality worldwide. Hypercholesterolemia is a chief risk factor for the progress of atherosclerotic vascular disease. Complementary and alter...
Cardiovascular diseases (CVD) are the prominent cause of mortality worldwide. Hypercholesterolemia is a chief risk factor for the progress of atherosclerotic vascular disease. Complementary and alternative medicine (CAM) such as herbal interventions has received much attention in literature. Rhus Coriaria (RC) with the general name Sumac is a medicinal spice, especially in Middle Eastern countries which is well known as an anti-lipid spice. This study aimed to summarize the existing findings regarding the effect of RC on the lipid profile. In this review randomized controlled trials (RCTs) assessing the effect of RC on blood lipids were included. Electronic searches using the MeSH terms were conducted in the following databases: Medline, Embase, Scopus, Web of Science and The Cochrane Library. The effect of RC on serum lipid concentration were measured as standardized mean difference (SMD) and 95% confidence intervals (CI) by the random-effects model. The initial search extracted 119 potentially relevant articles. After studying these publications, 4 were potentially eligible and retrieved in full text (four RCTs). Based on the results of the systematic review, RC has positive effects on different indices of the lipid profile including increasing Apo A-I and HDL; decreasing Apo B, Apo B/ Apo A1 ratio, total cholesterol, LDL and triglyceride. However the meta-analysis conducted on three studies on total cholesterol, HDL, LDL and triglyceride individually did not show any significant difference between intervention and control groups. No definite conclusion could be made on the effect of RC on serum blood lipids due to lack of sufficient clinical trials and variable inconsistency. Future trials with desirable designs that would eliminate the limitations in the current evidence are needed before conclusive claims can be made about the effect of RC on the lipid profile.
- Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice. [Journal Article]
- BRBiol Res 2018 Sep 15; 51(1):34
- CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
- Crystal structure of p-nitrophenol 4-monooxygenase PnpA from Pseudomonas putida DLL-E4: The key enzyme involved in p-nitrophenol degradation. [Journal Article]
- BBBiochem Biophys Res Commun 2018 Sep 11
- p-Nitrophenol 4-monooxygenase PnpA, the key enzyme in the hydroquinone pathway of p-nitrophenol (PNP) degradation, catalyzes the monooxygenase reaction of PNP to p-benzoquinone in the presence of FAD...
p-Nitrophenol 4-monooxygenase PnpA, the key enzyme in the hydroquinone pathway of p-nitrophenol (PNP) degradation, catalyzes the monooxygenase reaction of PNP to p-benzoquinone in the presence of FAD and NADH. Here, we determined the first crystal structure of PnpA from Pseudomonas putida DLL-E4 in its apo and FAD-complex forms to a resolution of 2.04 Å and 2.48 Å, respectively. The PnpA structure shares a common fold with hydroxybenzoate hydroxylases, despite a low amino sequence identity of 14-18%, confirming it to be a member of the Class A flavoprotein monooxygenases. However, substrate docking studies of PnpA indicated that the residues stabilizing the substrate in an orientation suitable for catalysis are not observed in other homologous hydroxybenzoate hydroxylases, suggesting PnpA employs a unique catalytic mechanism. This work expands our understanding on the reaction mode for this enzyme class.
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- Cloning and Expression of a Nonribosomal Peptide Synthetase to Generate Blue Rose. [Journal Article]
- ASACS Synth Biol 2018 Sep 18
- Rose has been entwined with human culture and history. "Blue rose" in English signifies unattainable hope or an impossible mission as it does not exist naturally and is not breedable regardless of ce...
Rose has been entwined with human culture and history. "Blue rose" in English signifies unattainable hope or an impossible mission as it does not exist naturally and is not breedable regardless of centuries of effort by gardeners. With the knowledge of genes and enzymes involved in flower pigmentation and modern genetic technologies, synthetic biologists have undertaken the challenge of producing blue rose by engineering the complicated vacuolar flavonoid pigmentation pathway and resulted in a mauve-colored rose. A completely different strategy presented in this study employs a dual expression plasmid containing bacterial idgS and sfp genes. The holo-IdgS, activated by Sfp from its apo-form, is a functional nonribosomal peptide synthetase that converts l-glutamine into the blue pigment indigoidine. Expression of these genes upon petal injection with agro-infiltration solution generates blue-hued rose flowers. We envision that implementing this proof-of-concept with obligatory modifications may have tremendous impact in floriculture to achieve a historic milestone in rose breeding.