Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus. Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S-methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to S-adenosylhomocysteine (1.33 Å) and GtmA complexed to S-adenosylmethionine (2.28 Å), providing mechanistic insights into this important biotransformation. We further reveal that simultaneous elimination of the ability of A. fumigatus to dissipate highly reactive dithiol gliotoxin, via deletion of GliT and GtmA, results in the most significant hypersensitivity to exogenous gliotoxin observed to date. Indeed, quantitative proteomic analysis of ΔgliT::ΔgtmA reveals an uncontrolled over-activation of the gli-cluster upon gliotoxin exposure. The data presented herein reveal, for the first time, the extreme risk associated with intracellular dithiol gliotoxin biosynthesis—in the absence of an efficient dismutation capacity. Significantly, a previously concealed protective role for GtmA and functionality of ETP bis-thiomethylation as an ancestral protection strategy against dithiol compounds is now evident.
Isovaleryl coenzyme A (IV-CoA) is an important precursor for iso-fatty acids and lipids. It acts in the development of myxobacteria, which can produce this compound from acetyl-CoA through alternative IV-CoA biosynthesis (aib). A central reaction of aib is catalyzed by AibA/AibB, which acts as a cofactor-free decarboxylase despite belonging to the family of CoA-transferases. We developed an efficient expression system for AibA/AibB that allowed the determination of high-resolution crystal structures in complex with different ligands. Through mutational studies, we show that an active-site cysteine previously proposed to be involved in decarboxylation is not required for activity. Instead, AibA/AibB seems to induce an intramolecular decarboxylation by binding its substrate in a hydrophobic cavity and forcing it into a bent conformation. Our study opens opportunities for synthetic biology studies, since AibA/AibB may be suitable for the production of isobutene, a precursor of biofuels and chemicals.
Photodiodes are used as easy-to-operate detectors in the extreme-ultraviolet spectral range. At the Physikalisch-Technische Bundesanstalt photodiodes are calibrated with an uncertainty of spectral responsivity of 0.3% or less. Stable photodiodes are a prerequisite for the dissemination of these high-accuracy calibrations to customers. Silicon photodiodes with different top layers were exposed to intense extreme-ultraviolet irradiation. Diodes coated with diamondlike carbon or TiSiN proved to be stable within a few percent up to a radiant exposure of 100 kJ/cm2. The changes in responsivity could be explained as being due to carbon contamination and to changes in the internal charge collection efficiency. In ultrahigh vacuum, no indication of oxidation was found.
The report summarizes the Consultative Committee for Mass (CCM) key comparison CCM.P-K4.2012 for absolute pressure spanning the range of 1 Pa to 10 000 Pa. The comparison was carried out at six National Metrology Institutes (NMIs), including National Institute of Standards and Technology (NIST), Physikalisch-Technische Bundesanstalt (PTB), Czech Metrology Institute (CMI), National Metrology Institute of Japan (NMIJ), Centro Nacional de Metrología (CENAM), and DI Mendeleyev Institute for Metrology (VNIIM). The comparison was made via a calibrated transfer standard measured at each of the NMIs facilities using their laboratory standard during the period May 2012 to September 2013. The transfer package constructed for this comparison preformed as designed and provided a stable artifact to compare laboratory standards. Overall the participants were found to be statistically equivalent to the key comparison reference value.
The aim of this paper is to give architects and engineers who are involved in the design of buildings and components certain guidelines for the "robot-oriented design and re-design" in order to support further spread of robotic technology in construction. Most of the construction and building costs are determined at the design stage. Final on-site construction operations should already be considered at the design stage of buildings and elements. Modern buildings consist of many subsystems, a coordination of all building subsystems is necessary considering constraints of robotic technology. In order to establish determined conditions for robotic on-site operations, the elements of building subsystems have to be geometrically and physically well defined. The problem of varying accuracies can be controlled by designing a compliant building system. The assembly stage is one of the final production phases before the product can be utilized and therefore the shorter the on-site assembly lasts, the higher the profitability of the building becomes. I I nI Fixed Cost Li Accrued Cost Orion Cost 18% Development Planning Design Production Disposition Organization Material Marketing High Lov -135-Graph 2 Evaluation and manipulation of cost during design process I Possibility of Cost-Manipulation 2 Possibility of Cost -Evaluation 3 Working La penOiture during Design Cost for Changes,Alterations Concepting Designing Detailling h _
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.