Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: Crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum

NAPc2, an anticoagulant protein from the hematophagous nematode Ancylostoma caninum evaluated in phase-II/IIa clinical trials, inhibits the extrinsic blood coagulation pathway by a two step mechanism, initially interacting with the hitherto uncharacterized factor Xa exosite involved in macromolecular recognition and subsequently inhibiting factor VIIa (K-i = 8.4 pM) of the factor VIIa/tissue factor complex. NAPc2 is highly flexible, becoming partially ordered and undergoing significant structural changes in the C terminus upon binding to the factor Xa exosite. In the crystal structure of the ternary factor Xa/NAPc2/selectide complex, the binding interface consists of an intermolecular antiparallel beta-sheet formed by the segment of the polypeptide chain consisting of residues 74-80 of NAPc2 with the residues 86-93 of factor Xa that is additional maintained by contacts between the short helical segment (residues 67-73) and a turn (residues 26-29) of NAPc2 with the short C-terminal helix of factor Xa (residues 233-243). This exosite is physiologically highly relevant for the recognition and inhibition of factor X/Xa by macromolecular substrates and provides a structural motif for the development of a new class of inhibitors for the treatment of deep vein thrombosis and angioplasty. (c) 2006 Elsevier Ltd. All rights reserved.

Structure of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase from Pseudomonas putida

2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase from Pseudomonas putida is a key enzyme in the Entner-Doudoroff pathway which catalyses the cleavage of KDPG via a class I Schiff-base mechanism. The crystal structure of this enzyme has been refined to a crystallographic residual R = 17.1% (R-free = 21.4%). The N-terminal helix caps one side of the torus of the (betaalpha)(8)-barrel and the active site is located on the opposite, carboxylic side of the barrel. The Schiff-base-forming Lys145 is coordinated by a sulfate (or phosphate) ion and two solvent water molecules. The interactions that stabilize the trimer are predominantly hydrophobic, with the exception of the cyclically permuted bonds formed between Glu132 OE1 of one molecule and Thr129 OG1 of a symmetry-equivalent molecule. Except for the N-terminal helix, the structure of KDPG aldolase from P. putida closely resembles the structure of the homologous enzyme from Escherichia coli.

Crystal structure of a dimeric Ser49 PLA(2)-like myotoxic component of the Vipera ammodytes meridionalis venomics reveals determinants of myotoxicity and membrane damaging activity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The Origin of Nonmonotonic Complex Behavior and the Effects of Nonnative Interactions on the Diffusive Properties of Protein Folding

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The role of the vagus nerve in the generation of cardiorespiratory interactions in a neotropical fish, the pacu, Piaractus mesopotamicus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Vector and axial-vector correlators in a non-local chiral quark model

The behavior of the non-perturbative parts of the isovector-vector and isovector and isosinglet axial-vector correlators at Euclidean momenta is studied in the framework of a covariant chiral quark model with non-local quark-quark interactions. The gauge covariance is ensured with the help of the P-exponents, with the corresponding modification of the quark-current interaction vertices taken into account. The low- and high-momentum behavior of the correlators is compared with the chiral perturbation theory and with the QCD operator product expansion, respectively. The V-A combination of the correlators obtained in the model reproduces quantitatively the ALEPH and OPAL data on hadronic tau decays, transformed into the Euclidean domain via dispersion relations. The predictions for the electromagnetic pi(+/-) - pi(0) mass difference and for the pion electric polarizability are also in agreement with the experimental values. The topological susceptibility of the vacuum is evaluated as a function of the momentum, and its first moment is predicted to be chi'(0) approximate to (50 MeV)(2). In addition, the fulfillment of the Crewther theorem is demonstrated.

Recursive renormalization of the singlet one-pion-exchange plus point-like interactions

The subtracted kernel approach is shown to be a powerful method to be implemented recursively in scattering equations with regular plus point-like interactions. The advantages of the method allows one to recursively renormalize the potentials, with higher derivatives of the Dirac-delta, improving previous results. The applicability of the method is verified in the calculation of the 1 So nucleon-nucleon phase-shifts, when considering a potential with one-pion-exchange plus a contact interaction and its derivatives. The S-1(0) renormalization parameters are fitted to the data. The method can in principle be extended to any derivative order of the contact interaction, to higher partial waves and to coupled channels. (c) 2005 Elsevier B.V. All rights reserved.

Regular and chaotic interactions of two BPS dyons at low energy

We identify and analyze quasiperiodic and chaotic motion patterns in the time evolution of a classical, non-Abelian Bogomol'nyi-Prasad-Sommerfield (BPS) dyon pair at low energies. This system is amenable to the geodesic approximation which restricts the underlying SU(2) Yang-Mills-Higgs dynamics to an eight-dimensional phase space. We numerically calculate a representative set of long-time solutions to the corresponding Hamilton equations and analyze quasiperiodic and chaotic phase space regions by means of Poincare surfaces of section, high-resolution power spectra and Lyapunov exponents. Our results provide clear evidence for both quasiperiodic and chaotic behavior and characterize it quantitatively. Indications for intermittency are also discussed.

Probing intermediate mass Higgs interactions at the CERN large hadron collider

We analyze the potentiality of the CERN Large Hadron Collider to probe the Higgs boson couplings to the electroweak gauge bosons. We parametrize the possible deviations of these couplings due to new physics in a model independent way, using the most general dimension-six effective lagrangian where the SU(2)(L) x U(1)(Y) is realized linearly. For intermediate Higgs masses, the decay channel into two photons is the most important one for Higgs searches at the LHC, We study the effects of these new interactions on the Higgs production mechanism and its subsequent decay into two photons. We show that the LHC will be sensitive to new physics scales beyond the present limits extracted from the LEP and Tevatron physics. (C) 2000 Elsevier B.V. B,V, All rights reserved.

Stability analysis of the D-dimensional nonlinear Schrodinger equation with trap and two- and three-body interactions

Considering the static solutions of the D-dimensional nonlinear Schrodinger equation with trap and attractive two-body interactions, the existence of stable solutions is limited to a maximum critical number of particles, when D greater than or equal to 2. In case D = 2, we compare the variational approach with the exact numerical calculations. We show that, the addition of a positive three-body interaction allows stable solutions beyond the critical number. In this case, we also introduce a dynamical analysis of the conditions for the collapse. (C) 2000 Published by Elsevier B.V. B.V. All rights reserved.

Duffin-Kemmer-Petiau and Klein-Cordon-Fock equations for electromagnetic, Yang-Mills and external gravitational field interactions: proof of equivalence

Starting from the Generating functional for the Green Function (GF), constructed from the Lagrangian action in the Duffin-Kemmer-Petiau (DKP) theory (L-approach) we strictly prove that the physical matrix elements of the S-matrix in DKP and Klein-Gordon-Fock (KGF) theories coincide in cases of interacting spin O particles with external and quantized Maxwell and Yang-Mills fields and in case of external gravitational field (without or with torsion), For the proof we use the reduction formulas of Lehmann, Symanzik and Zimmermann (LSZ). We prove that many photons and Yang-Mills particles GF coincide in both theories too. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Study of W boson production in PbPb and pp collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Double parton interactions in gamma+3 jet events in p(p)over-bar collisions at root s=1.96 TeV

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Measurement of sin(2)theta(l)(eff) and Z-light quark couplings using the forward-backward charge asymmetry in p(p)over-bar -> Z/gamma* -> e(+)e(-) events with L=5.0 fb(-1) at root s=1.96 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

On energy transfer between vibrating systems under linear and nonlinear interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)