Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

The role of acetylated cyclooxygenase-2 in the biosynthesis of resolvin precursors derived from eicosapentaenoic acid

Specialized pro-resolving lipid mediators (SPMs) are natural bioactive agents actively involved in inflammation resolution. SPMs act when uncontrolled inflammatory processes are developed, for instance, in patients of COVID-19 or other diseases. The so-called resolution pharmacology aims at developing new treatments based on the use of SPMs as agonists, which promote inflammation resolution without unwanted side effects. It has been shown that the biosynthesis of SPMs called eicosapentaenoic acid (EPA)-derived E-series resolvins is initiated by aspirin-acetylated COX-2 from EPA, leading to 18-hydroperoxy-eicosapentaenoic acid (18-HpEPE). However, there are many open questions concerning the intriguing role of aspirin in the molecular mechanism of resolvin formation. Our MD simulations, combined with QM/MM calculations, show that the potential energy barriers for the H16-abstraction from EPA, required for forming 18-HpEPE, are higher than for the H13-abstraction, thus explaining why 18-HpEPE is a marginal product of COX-2 catalysis. By contrast, in the aspirin-acetylated COX-2/EPA complex, the H16proS-abstraction energy barriers are somewhat lower than the H13proS energy barriers and much smaller than the H16-transfer barriers in the wild type COX-2/EPA system. Those results agree with the experimental observation that aspirin favours the synthesis of several SPMs known as aspirin-triggered resolvins. In the following step of the catalytic mechanism, the calculated O2 addition to C18 is preferred versus the addition to C14 which also agrees with 18R-HEPE and 18S-HEPE being the main products from EPA in aspirin-acetylated COX-2

Role of Arg403 for thermostability and catalytic activity of rabbit 12/15-lipoxygenase.

12/15-Lipoxygenases (12/15-LOX) have been implicated in inflammatory and hyperproliferative diseases but the numerous aspects of structural biology of these enzymes are far from clear. Early mutagenesis data and structural modeling of enzyme-substrate complexes suggested that Arg403, which is localized at the entrance of the putative substrate binding pocket, might interact with the fatty acid carboxylic group. On the other hand, side-chain of Arg403 is a part of an ionic network with the residues of α2-helix, which undergoes pronounced conformation changes upon inhibitor binding. To explore the role of Arg403 for catalysis in more detail we exchanged positively charged Arg403 to neutral Leu and quantified structural and functional consequences of the alteration at the site of mutation using fluorometric techniques. We found that a loss of electrostatic interaction between Arg403 and negatively charged amino acid residues of α2-helix has only minor impact on protein folding, but partially destabilized the tertiary structure of the enzyme. We hypothesize that interaction of Arg403 with the substrate's carboxylate might be involved in a complex mechanism triggering conformational changes of the α2-helix, which are required for formation of the catalytically competent dimer r12/15-LOX complex at pre-catalytic stages