Human Cytomegalovirus Protease: Why is the Dimer Required for Catalytic Activity?

Human cytomegalovirus (HCMV) is a pathogenic agent responsible for morbidity and mortality in immunocompromised and immunosuppressed individuals. HCMV encodes a serine protease that is essential for the production of infectious virions. In this work, we applied molecular dynamics (MD) simulations on HCMV protease models in order to investigate the experimentally observed (i) catalytic activity of the enzyme homodimer and (ii) induced-fit mechanism upon the binding of substrates and peptidyl inhibitors.

On the application of accelerated molecular dynamics to liquid water simulations.

Our group recently proposed a robust bias potential function that can be used in an efficient all-atom accelerated molecular dynamics (MD) approach to simulate the transition of high energy barriers without any advance knowledge of the potential-energy landscape. The main idea is to modify the potential-energy surface by adding a bias, or boost, potential in regions close to the local minima, such that all transitions rates are increased. By applying the accelerated MD simulation method to liquid water, we observed that this new simulation technique accelerates the molecular motion without losing its microscopic structure and equilibrium properties.

A lyophilized aqueous extract of Maytenus ilicifolia leaves inhibits histamine-mediated acid secretion in isolated frog gastric mucosa.

Lyophilized aqueous extract of Maytenus ilicifolia leaves (LAEMIL) is commonly used in Brazilian folk medicine in the treatment of dyspepsia as well as gastric ulcers. We have investigated the effect and the possible mechanism of action of the LAEMIL on acid secretion in isolated frog gastric mucosa incubated in an Ussing chamber. It was observed that LAEMIL (7-28 mg%) as well as cimetidine (125-4,000 microM), a well-known histamine H2 receptor antagonist, decreased basal acid secretion in a concentration-dependent manner.

The relationship between normative orthodontic treatment need and oral health-related quality of life.

Objectives: The first objective was to assess whether having had orthodontic treatment affected the levels of oral health-related quality of life impacts in Brazilian adolescents. A second objective was to assess the relationship between a normative clinical measure of orthodontic treatment need and two measures of oral health-related quality of life.

Methods: A cross-sectional study was conducted in Bauru, SP, Brazil, on 1675 randomly selected adolescents aged between 15 and 16 years.

Synthetic and theoretical studies on the reduction of electron withdrawing group conjugated olefins using the Hantzsch 1,4-dihydropyridine ester.

The Hantzsch 1,4-dihydropyridine ester (1) has been observed to be a useful selective reducing agent for the reduction of electron-withdrawing conjugated double bonds. The rate of this reaction was observed to be dependent upon the nature of the conjugated substituents and, consequently, the electronic nature of the unsaturated double bond. Theoretical calculations confirmed the importance of the HOMO-LUMO gap for this reaction and implicated a hydride transfer, agreeing with the experimentally observed reaction rate order.

Investigation of the induced-fit mechanism and catalytic activity of the human cytomegalovirus protease homodimer via molecular dynamics simulations.

Human cytomegalovirus (HCMV) is a highly species-specific DNA virus infecting up to 80% of the general population. The viral genome contains the open reading frame UL80, which encodes the full-length 80 kDa HCMV serine protease and its substrate. Full-length HCMV protease is composed of an N-terminal 256-amino-acid proteolytic domain, called assemblin, a linker region, and a C-terminal structural domain, the assembly protein precursor.

Quantitative assessment of nitric oxide in rat skeletal muscle and plasma after exercise.

Nitric oxide (NO), a short-lived vasoactive substance that has multiple physiological functions, is also involved in skeletal muscle physiology. This work examines the levels of nitrate (the metabolic end-product of NO) in muscle and plasma after different exercise protocols: namely acute, eccentric, cardiac stress and training. Plasma nitrate levels were augmented after strenuous exercise and did not change after training.

Metal ion complexation properties of fulvic acids extracted from composted sewage sludge as compared to a soil fulvic acid.

Complexation properties of an anthropogenic fulvic acid (FA) extracted from a composted sewage sludge (csFA) for Cu(II), Pb(II) and Cd(II) were studied at pH=6 and at a concentration of 25 mg L(-1). For the case of Cu(II), a particular analysis of the complexation phenomena was done at pH values of 3, 4, 5 and 6 and at aqueous FA concentrations of 25, 50 and 100 mg L(-1) by synchronous excitation molecular fluorescence spectroscopy (SyF). Potentiometric titrimetry with Cu(II), Pb(II), Cd(II) and H+ ion-selective electrodes and acid-base conductimetric titrations were used to obtain experimental information about the acid properties and complexation phenomena.