58 research outputs found
Active-site protonation states in an Acyl-Enzyme intermediate of a Class A β-Lactamase with a Monobactam Substrate
The monobactam antibiotic aztreonam is used to treat cystic fibrosis patients with chronic pulmonary infections colonized by Pseudomonas aeruginosa strains expressing CTX-M extended-spectrum β-lactamases. The protonation states of active-site residues that are responsible for hydrolysis have been determined previously for the apo form of a CTX-M β-lactamase but not for a monobactam acyl-enzyme intermediate. Here we used neutron and high-resolution X-ray crystallography to probe the mechanism by which CTX-M extended-spectrum β-lactamases hydrolyze monobactam antibiotics. In these first reported structures of a class A β-lactamase in an acyl-enzyme complex with aztreonam, we directly observed most of the hydrogen atoms (as deuterium) within the active site. Although Lys 234 is fully protonated in the acyl intermediate, we found that Lys 73 is neutral. These findings are consistent with Lys 73 being able to serve as a general base during the acylation part of the catalytic mechanism, as previously proposed
An Observational Overview of Solar Flares
We present an overview of solar flares and associated phenomena, drawing upon
a wide range of observational data primarily from the RHESSI era. Following an
introductory discussion and overview of the status of observational
capabilities, the article is split into topical sections which deal with
different areas of flare phenomena (footpoints and ribbons, coronal sources,
relationship to coronal mass ejections) and their interconnections. We also
discuss flare soft X-ray spectroscopy and the energetics of the process. The
emphasis is to describe the observations from multiple points of view, while
bearing in mind the models that link them to each other and to theory. The
present theoretical and observational understanding of solar flares is far from
complete, so we conclude with a brief discussion of models, and a list of
missing but important observations.Comment: This is an article for a monograph on the physics of solar flares,
inspired by RHESSI observations. The individual articles are to appear in
Space Science Reviews (2011
Recommended from our members
The reactions of neutral iron clusters with D/sub 2/O: Deconvolution of equilibrium constants from multiphoton processes
The chemical reactions of neutral iron clusters with D/sub 2/O are studied in a continuous flow tube reactor by molecular beam sampling and time-of-flight mass spectrometry with laser photoionization. Product distributions are invariant to a four-fold change in reaction time demonstrating that equilibrium is attained between free and adsorbed D/sub 2/O. The observed negative temperature dependence is consistent with an exothermic, molecular addition reaction at equilibrium. Under our experimental conditions, there is significant photodesorption of D/sub 2/O (Fe/sub n/(D/sub 2/O)/sub m/ + h..nu.. ..-->.. Fe/sub n/ + m D/sub 2/O) along with ionization due to absorption of multiple photons from the ionizing laser. Using a simple model based on a rate equation analysis, we are able to quantitatively deconvolute this desorption process from the equilibrium constants. 8 refs., 1 fig
Criteria for environmentally associated autoimmune diseases
Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future
- …