Mechanism of Acyl Transfer by the Class a Serine Beta-Lactamase of Streptomyces Albus G

in Biochemical Journal (1991), 279(Pt 1), 213-221

Optimization by energy minimization of stable complexes occurring along the pathway of hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase has highlighted a ... [more ▼]

Optimization by energy minimization of stable complexes occurring along the pathway of hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase has highlighted a proton shuttle that may explain the catalytic mechanism of the beta-lactamases of class A. Five residues, S70, S130, N132, T235 and A237, are involved in ligand binding. The gamma-OH group of T235 and, in the case of benzylpenicillin, the gamma-OH group of S130 interact with the carboxylate group, on one side of the ligand molecule. The side-chain NH2 group of N132 and the carbonyl backbone of A237 interact with the exocyclic CONH amide bond, on the other side of the ligand. The backbone NH groups of S70 and A237 polarize the carbonyl group of the scissile beta-lactam amide bond. Four residues, S70, K73, S130 and E166, and two water molecules, W1 and W2, perform hydrolysis of the bound beta-lactam compound. E166, via W1, abstracts the proton from the gamma-OH group of S70. While losing its proton, the O-gamma atom of S70 attacks the carbonyl carbon atom of the beta-lactam ring and, concomitantly, the proton is delivered back to the adjacent nitrogen atom via W2, K73 and S130, thus achieving formation of the acyl-enzyme. Subsequently, E166 abstracts a proton from W1. While losing its proton, W1 attacks the carbonyl carbon atom of the S70 ester-linked acyl-enzyme and, concomitantly, re-entry of a water molecule W'1 replacing W1 allows E166 to deliver the proton back to the same carbonyl carbon atom, thus achieving hydrolysis of the beta-lactam compound and enzyme recovery. The model well explains the differences found in the kcat. values for hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase. It also explains the effects caused by site-directed mutagenesis of the Bacillus cereus beta-lactamase I [Gibson, Christensen [less ▲]

Mechanism of Collisional Heating in Electrospray Mass Spectrometry: Ion Trajectory Calculations

in Journal of Physical Chemistry A (2001), 105

To simulate the multicollisional heating process taking place in the intermediate pressure region of an electrospray source, ion trajectory calculations have been preformed by introducing in the SIMION ... [more ▼]

To simulate the multicollisional heating process taking place in the intermediate pressure region of an electrospray source, ion trajectory calculations have been preformed by introducing in the SIMION program a subroutine for handling the collision dynamics. The simulated internal energy distributions are compared with already available experimental distributions obtained by the "survival ion yield" method. [less ▲]

Mechanism of improvement in mitral regurgitation after cardiac resynchronization therapy.

in European Heart Journal (2008), 29(6), 757-65

AIMS: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after ... [more ▼]

AIMS: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Sixty eight patients consecutive (LV ejection fraction 23 +/- 8%) with at least moderate MR (>or=grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 +/- 115 ms vs. 190 +/- 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders. CONCLUSION: Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT. [less ▲]

Mechanism of lipolysis in milk : a modelistic approach using Langmuir film balance.

Poster (2007, October 11)

The mechanism of polymer drag reduction

Scientific conference (2004, February)

Mechanism of Single-Electron Capture by the Dichlorocarbene Dication.

in Journal of the American Society for Mass Spectrometry (1996), 7

The single-electron capture (SEC) by dichlorocarbene with eight different atomic and molecular target gases, (CCl2)2++G->(CCl2)++G+, has been studied by product ion spectroscopy and ion kinetic energy ... [more ▼]

The single-electron capture (SEC) by dichlorocarbene with eight different atomic and molecular target gases, (CCl2)2++G->(CCl2)++G+, has been studied by product ion spectroscopy and ion kinetic energy spectroscopy. The experimental data have been interpreted in the framework of a theoretical model that describes the charge exchange process. Exothermic charge exchange is handled within the Landau-Zener model, whereas endothermic charge exchange is described by the Demkov model. The calculated data reproduce qualitatively the essential features of the experimental results: (1) the appearance of a reaction window centered at an exothermicity in the 4-4.5 eV range, (2) the lower SEC cross sections for endothermic charge exchange, (3) the wider internal energy distributions obtained for CCl2+ in the endothermic regime than in the exothermic one, which results in larger dissociation yields, (4) the excitation of molecular targets that accompany their ionization in the SEC process, and (5) the kinetic energy released on the CCl++Cl fragments in dissociative SEC. [less ▲]

Mechanism of sound production in Oreochromis niloticus

Poster (2007)

Mechanism of the exchanges catalysed by the oxoglutarate translocator of rat-heart mitochondria. Kinetics of the external-product inhibition.

in Archives Internationales de Physiologie et de Biochimie (1973), 81

Mechanism of tumor reoxygenation after anti-angiogenic therapy using SU5416 and its importance for guiding combined anti-tumor therapy

in International Journal of Cancer Research (2006), (66(19)), 9698-9704

Emerging preclinical studies support the concept of a transient ‘‘normalization’’ of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated ... [more ▼]

Emerging preclinical studies support the concept of a transient ‘‘normalization’’ of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated radiotherapy or chemotherapy. One key issue in this area of research is to determine whether this feature is common to all antiangiogenic drugs and whether the phenomenon occurs in all types of tumors. In the present study, we characterized the evolution of the tumor oxygenation (in transplantable liver tumor and FSAII tumor models) after administration of SU5416, an antagonist of the vascular endothelial growth factor receptor. SU5416 induced an early increase in tumor oxygenation [measured by electronic paramagnetic resonance (EPR)], which did not correlate with remodeling of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry) or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration (measured by EPR) was responsible for this early reoxygenation. Consistent with these unique findings in the tumor microenvironment, we found that SU5416 potentiated tumor response to radiotherapy but not to chemotherapy. In addition to the fact that the characterization of the tumor oxygenation is essential to enable correct application of combined therapies, our results show that the long-term inhibition of oxygen consumption is a potential novel target in this class of compounds. (Cancer Res 2006; 66(19): 9698-704 [less ▲]

Mechanisms controlling the oxygen consumption in experimentally induced hypochloremic alkalosis in calves

in Veterinary Research (2002), 33

The study was carried out on healthy Friesian calves (n = 10) aged between 10 and 30 days. Hypochloremia and alkalosis were induced by intravenous administration of furosemide and isotonic sodium ... [more ▼]

The study was carried out on healthy Friesian calves (n = 10) aged between 10 and 30 days. Hypochloremia and alkalosis were induced by intravenous administration of furosemide and isotonic sodium bicarbonate. The venous and arterial blood samples were collected repeatedly. 2,3-diphosphoglycerate (2,3-DPG), hemoglobin and plasmatic chloride concentrations were determined. The red blood cell chloride concentration was also calculated. pH, PCO2 and PO2 were measured in arterial and mixed venous blood. The oxygen equilibrium curve (OEC) was measured in standard conditions. The correspondence of the OEC to the arterial and mixed venous compartments was calculated, taking blood temperature, pH and PCO2 values into account. The oxygen exchange fraction (OEF%), corresponding to the degree of blood desaturation between the arterial and mixed venous compartments and the amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated from the arterial and mixed venous OEC, combined with PO2 and hemoglobin concentration. Oxygen delivery (DO2) was calculated using the arterial oxygen content, the cardiac output measured by thermodilution, and the body weight of the animal. The oxygen consumption (VO2) was derived from the cardiac output, OEF Vol% and body weight values. Despite the plasma hypochloremia, the erythrocyte chloride concentration was not influenced by furosemide and sodium bicarbonate infusion. Due to the alkalosis-induced increase in the 2,3-DPG, the standard OEC was shifted to the right, allowing oxygen to dissociate from hemoglobin more rapidly. These changes opposed the increased affinity of hemoglobin for oxygen induced by alkalosis. Moreover, respiratory acidosis, hemoconcentration, and the slight decrease in the partial oxygen pressure in mixed venous blood (Pvo(2)) tended to improve the OEF Vol% and maintain the oxygen consumption in a physiological range while the cardiac output, and the oxygen delivery were significantly decreased. It may be concluded that, despite reduced oxygen delivery, oxygen consumption is maintained during experimentally induced hypochloremic alkalosis in healthy 10-30 day old calves [less ▲]