title: Why do divalent metal ions either promote or inhibit enzymatic reactions? The case of BamHI restriction endonuclease from combined quantum-classical simulations.
abstract: Divalent metal ions are essential to many enzymatic reactions involving nucleic acids, but their critical and specific role still needs to be uncovered. Restriction endonucleases are a prominent group of such metal-requiring enzymes. Large scale accurate simulations of Mg- and Ca-BamHI elucidate the mechanism of the catalytic reaction leading to DNA cleavage and show that it involves the concerted action of two metal ions and water molecules. It is also established that what is decisive for the dramatically different behavior of magnesium (a cocatalyst) and calcium (an inhibitor) are kinetic factors and not the properties of the prereactive states of the enzymes. A new perspective is opened for the understanding of the functional role of metal ions in biological processes.
authors.affiliation: IBM Research, Zurich Research Laboratory, 8803 Rüschlikon, Switzerland.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mordasini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Curioni
authors.forename: Wanda
authors.initials: W
authors.lastname: Andreoni
mesh_terms: D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism; D015245:Deoxyribonuclease BamHI / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D055672:Static Electricity
chemical_list: D002413:Cations, Divalent; D008670:Metals; D004247:DNA; D015245:Deoxyribonuclease BamHI; D008274:Magnesium; D002118:Calcium