Track topics on Twitter Track topics that are important to you
The presence of Fe-bound cyanide ligands in the active site of the proton-reducing enzymes [FeFe]-hydrogenases has led to the hypothesis that such Brønsted-Lowry bases could be protonated during the catalytic cycle, thus implying that hydrogen isocyanide (HNC) might have a relevant role in such crucial microbial metabolic paths. We present a hybrid quantum mechanical/molecular mechanical (QM/MM) study of the energetics of CN(-) protonation in the enzyme, and of the effects that cyanide protonation can have on [FeFe]-hydrogenase active sites. A detailed analysis of the electronic properties of the models and of the energy profile associated with H(2) evolution clearly shows that such protonation is dysfunctional for the catalytic process. However, the inclusion of the protein matrix surrounding the active site in our QM/MM models allowed us to demonstrate that the amino acid environment was finely selected through evolution, specifically to lower the Brønsted-Lowry basicity of the cyanide ligands. In fact, the conserved hydrogen-bonding network formed by these ligands and the neighboring amino acid residues is able to impede CN(-) protonation, as shown by the fact that the isocyanide forms of [FeFe]-hydrogenases do not correspond to stationary points on the enzyme QM/MM potential-energy surface.
Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della Scienza 2, 20126, Milan (Italy), Fax: (+39) 02-6448-3478. Claudio.firstname.lastname@example.org.
This article was published in the following journal.
Name: Chemistry (Weinheim an der Bergstrasse, Germany)
Myoglobins reconstituted with aqua- and cyano-Co(III) tetradehydrocorrins, rMb(Co(III)(OH2)(TDHC)) and rMb(Co(III)(CN)(TDHC)), respectively, were prepared and investigated as models of a cobalamin-dep...
We demonstrate Fourier transform (FT) 2D vibrational-electronic (2D VE) spectroscopy employing a novel mid-IR and optical pulse sequence. This new femtosecond third-order nonlinear spectroscopy provid...
Geometrical optimizations of the ground and first excited states of benzimidazole and indene were performed using the density functional theory (DFT) and its time-dependent extension methods (TD-DFT),...
The synthesis of six new bis(cyano) iron(III) porphyrinate derivatives is reported. The anionic porphyrin complexes utilized tetraphenylporphyrin, tetramesitylporphyrin, and tetratolylporphyrin as the...
Cyanide, one of the known most toxic chemicals, is widely used in mining and jewellery industries for gold extraction and recovery from crushed ores or electroplating residues. Cyanide toxicity occurs...
People who has been in a fire accident have been shown often to be cyanide poisoned as well as poisoned with carbon monoxide(CO). According to recommendations from the Danish Health Agency...
This randomized pilot clinical trial studies the effects of electronic cigarettes on the lungs. Studying the effects of electronic cigarettes on the lungs may provide the Food and Drug Adm...
The purpose of this study is to measure plasma nicotine uptake parameters, physiological measures, and subjective effect measures in smokers during and following a single ad libitum use of...
The purpose of this study is to learn more about nicotine exposure and the safety of electronic cigarettes (EC). It will focus on the areas that are thought to most closely relate to the a...
This study assesses the nicotine pharmacokinetic (PK) parameters in adopters of electronic cigarettes following a 12-hour tobacco and nicotine abstinence. The PK results of this study will...
Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
Theoretical representations that simulate the behavior or activity of the cardiovascular system, processes, or phenomena; includes the use of mathematical equations, computers and other electronic equipment.
Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...