Catalytic specificity and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa

: The escalating drug resistance among microorganisms underscores the urgent need for innovative therapeutic strategies and a comprehensive understanding of bacteria's defense mechanisms against oxidative stress and antibiotics. Among the recently discovered barriers, the endogenous production of hydrogen sulfide (H2S) via the reverse transsulfuration pathway, emerges as a noteworthy factor. In this study, we have explored the catalytic capabilities and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa (PaCGL), a multidrug-opportunistic pathogen chiefly responsible for nosocomial infections. In addition to a canonical L-cystathionine hydrolysis, PaCGL efficiently catalyzes the production of H2S using L-cysteine and/or L-homocysteine as alternative substrates. Comparative analysis with the human enzyme and counterparts from other pathogens revealed distinct structural features within the primary enzyme cavities. Specifically, a distinctly folded entrance loop could potentially modulate the access of substrates and/or inhibitors to the catalytic site. Our findings offer significant insights into the structural evolution of CGL enzymes across different pathogens and provide novel opportunities for developing specific inhibitors targeting PaCGL

Mutation of Ser-50 and Cys-66 in Snapin Modulates Protein Structure and Stability

Snapin is a 15 kDa protein present in neuronal and non-neuronal cells that has been implicated in the regulation of exocytosis and endocytosis. Protein kinase A (PKA) phosphorylates Snapin at Ser-50, modulating its function. Likewise, mutation of Cys-66, which mediates protein dimerization, impairs its cellular activity. Here, we have investigated the impact of mutating these two positions on protein oligomerization, structure, and thermal stability, along with the interaction with SNARE proteins. We found that recombinant purified Snapin in solution appears mainly as dimers in equilibrium with tetramers. The protein exhibits modest secondary structure elements and notable thermal stability. Mutation of Cys-66 to Ser abolished subunit dimerization, but not higher-order oligomers. This mutant augmented the presence of α-helical structure and slightly increased the protein thermal stability. Similarly, the S50A mutant, mimicking the unphosphorylated protein, also exhibited a higher helical secondary structure content than the wild type, along with greater thermal stability. In contrast, replacement of Ser-50 with Asp (S50D), emulating the protein-phosphorylated state, produced a loss of α-helical structure, concomitant with a decrease in protein thermal stability. In vitro, the wild type and mutants weakly interacted with SNAP-25 and the reconstituted SNARE complex, although S50D exhibited the strongest binding to the SNARE complex, consistent with the observed higher cellular activity of PKA-phosphorylated Snapin. Our observations suggest that the stronger binding of S50D to SNAREs might be due to a destabilization of tetrameric assemblies of Snapin that favor the interaction of protein dimers with the SNARE proteins. Therefore, phosphorylation of Ser-50 has an important impact on the protein structure and stability that appears to underlie its functional modulation

Search for high-mass resonances decaying to a jet and a Lorentz-boosted resonance in proton-proton collisions at $\sqrt{s}=13\text{ }\text{ }\mathrm{TeV}

Physics letters / B 832, 137263 (2022). doi:10.1016/j.physletb.2022.137263 Published by North-Holland Publ., Amsterda

Two-particle Bose-Einstein correlations and their Lévy parameters in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

Two-particle Bose-Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV. The data sample, containing 4.27$\times10^{9}$ minimum bias events corresponding to an integrated luminosity of 0.607 nb$^{-1}$, was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a L\'evy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the L\'evy index or shape parameter ($\alpha$), the L\'evy scale parameter ($R$), and the correlation strength parameter ($\lambda$). The source shape, characterized by $\alpha$, is found to be neither Cauchy nor Gaussian, implying the need for a full L\'evy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the L\'evy $R$ parameter. The $\lambda$ parameter is studied in terms of the core-halo model.Comment: Submitted to Physical Review C. All figures and tables can be found at http://cms-results.web.cern.ch/cms-results/public-results/publications/HIN-21-011 (CMS Public Pages

Search for supersymmetry in hadronic final states with missing transverse energy using the variables αT and b-quark multiplicity in pp collisions at √s = 8 TeV

Submitted by Vitor Silverio Rodrigues ([email protected]) on 2014-05-27T11:30:34Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:48:49Z : No. of bitstreams: 1 2-s2.0-84883824987.pdf: 1540579 bytes, checksum: be6bbff5192436d9fcdbc367ffd1650e (MD5) Made available in DSpace on 2014-05-27T11:30:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-01 An inclusive search for supersymmetric processes that produce final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of 8 TeV. The data sample corresponds to an integrated luminosity of 11.7 fb-1 collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, αT, is used to discriminate between events with genuine and misreconstructed missing transverse energy. The search is based on an examination of the number of reconstructed jets per event, the scalar sum of transverse energies of these jets, and the number of these jets identified as originating from bottom quarks. No significant excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of simplified models, with a special emphasis on both compressed-spectrum scenarios and direct or gluino-induced production of third-generation squarks. For the case of gluino-mediated squark production, gluino masses up to 950-1125 GeV are excluded depending on the assumed model. For the direct pair-production of squarks, masses up to 450 GeV are excluded for a single light first- or second-generation squark, increasing to 600 GeV for bottom squarks. © 2013 CERN for the benefit of the CMS collaboration. CERN, Geneva Yerevan Physics Institute, Yerevan Institut für Hochenergiephysik der OeAW, Wien National Centre for Particle and High Energy Physics, Minsk Universiteit Antwerpen, Antwerpen Vrije Universiteit Brussel, Brussel Université Libre de Bruxelles, Bruxelles Ghent University, Ghent Université Catholique de Louvain, Louvain-la-Neuve Université de Mons, Mons Centro Brasileiro de Pesquisas Fisicas, Rio de Janeiro Universidade do Estado do Rio de Janeiro, Rio de Janeiro Universidade Estadual Paulista, São Paulo Universidade Federal do ABC, São Paulo Institute for Nuclear Research and Nuclear Energy, Sofia University of Sofia, Sofia Institute of High Energy Physics, Beijing State Key Laboratory of Nuclear Physics and Technology Peking University, Beijing Universidad de Los Andes, Bogota Technical University of Split, Split University of Split, Split Institute Rudjer Boskovic, Zagreb University of Cyprus, Nicosia Charles University, Prague Academy of Scientific Research and Technology of the Arab Republic of Egypt Egyptian Network of High Energy Physics, Cairo National Institute of Chemical Physics and Biophysics, Tallinn Department of Physics University of Helsinki, Helsinki Helsinki Institute of Physics, Helsinki Lappeenranta University of Technology, Lappeenranta DSM/IRFU CEA/Saclay, Gif-sur-Yvette Laboratoire Leprince-Ringuet, Ecole Polytechnique IN2P3-CNRS, Palaiseau Institut Pluridisciplinaire Hubert Curien, Universite de Strasbourg, Universite de Haute Alsace Mulh CNRS/IN2P3, Strasbourg CNRS-IN2P3, Institut de Physique Nucléaire de Lyon Université de Lyon, Université Claude Bernard Lyon 1, Villeurbanne Institute of High Energy Physics and Informatization Tbilisi State University, Tbilisi I. 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