caa a22 4500 445878304 CHVBK 20180317145534.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s11030-010-9256-3 doi (NATIONALLICENCE)springer-10.1007/s11030-010-9256-3 Impact of Mercury(II) on proteinase K catalytic center: investigations via classical and Born-Oppenheimer molecular dynamics [Elektronische Daten] [Jarosław Panek, Riccardo Mazzarello, Marjana Novič, Aneta Jezierska-Mazzarello] Mercury(II) has a strong affinity for the thiol groups in proteins often resulting in the disruption of their biological functions. In this study we present classical and first-principles, DFT-based molecular dynamics (MD) simulations of a complex of Hg(II) and proteinase K, a well-known serine protease with a very broad and diverse enzymatic activity. It contains a catalytic triad formed by Asp39, His69, and Ser224, which is responsible for its biological activity. It was found previously by X-ray diffraction experiments that the presence of Hg(II) inhibits the enzymatic action of proteinase K by affecting the stereochemistry of the triad. Our simulations predict that (i) the overall structure as well as the protein backbone dynamics are only slightly affected by the mercury cation, (ii) depending on the occupied mercury site, the hydrogen bonds of the catalytic triad are either severely disrupted (both bonds for mercury at site 1, and the His69-Ser224 contact for mercury at site 2) or slightly strengthened (the Asp39-His69 bond when mercury is at site 2), (iii) the network of hydrogen bonds of the catalytic triad is not static but undergoes constant fluctuations, which are significantly modified by the presence of the Hg(II) cation, influencing in turn the triad's ability to carry out the enzymatic function—these facts explain the experimental findings on the inhibition of proteinase K by Hg(II). Springer Science+Business Media B.V., 2010 Proteinase K nationallicence Hg(II) nationallicence Catalytic triad nationallicence Classical MD nationallicence Ab initio MD nationallicence Panek Jarosław Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland aut Mazzarello Riccardo Computational Science, Department of Chemistry and Applied Biosciences, ETH Zurich, USI Campus, via Giuseppe Buffi 13, 6900, Lugano, Switzerland aut Novič Marjana National Institute of Chemistry, Hajdrihova 19, 1001, Ljubljana, Slovenia aut Jezierska-Mazzarello Aneta Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland aut Molecular Diversity Springer Netherlands 15/1(2011-02-01), 215-226 1381-1991 15:1<215 2011 15 11030 https://doi.org/10.1007/s11030-010-9256-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9256-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Panek Jarosław Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland aut NATIONALLICENCE 700 1- Mazzarello Riccardo Computational Science, Department of Chemistry and Applied Biosciences, ETH Zurich, USI Campus, via Giuseppe Buffi 13, 6900, Lugano, Switzerland aut NATIONALLICENCE 700 1- Novič Marjana National Institute of Chemistry, Hajdrihova 19, 1001, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Jezierska-Mazzarello Aneta Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/1(2011-02-01), 215-226 1381-1991 15:1<215 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer