Mg spin affects adenosinetriphosphate activity

The Schlegel-Frisch ab initio molecular dynamics (ADMP) (DFT:B3LYP), T = 310 K, is used to study complexation between adenosinetriphosphate (ATP), ATP subsystem, and magnesium cofactor [Mg(H2O)6] , Mg subsystem, in a water pool, modeled with 78 water molecules, in singlet (S) and triplet (T) states. The computations prove that the way of ATP cleavage is governed by the electron spin of Mg. In the S state Mg prefers chelation of -phosphate oxygens (O1-O2), whereas in the T state it chelates --phosphate oxygens (O2-O3) or produces a single-bonded intermediate. Unlike the chelates, which initiate ionic reaction paths, the single-bonded intermediate starts off a free-radical path of ATP cleavage, yielding a highly reactive adenosinemonophosphate ion-radical, •AMP, earlier observed in the CIDNP (Chemically Induced Dynamic Nuclear Polarization) experiment (A.A. Tulub, 2006). The free-radical path is highly sensitive to Mg nuclear spin, which through a hyperfine interaction favors the production of unpaired electron spins. The unique role of Mg in ATP cleavage comes through its ability to serve as a unique redox center, initially accepting an electron from ATP and then giving it back to products. Redox activity of Mg differs for T and S states and affects the number of coordinated water molecules. The findings give a new insight into the NTP (N = nucleoside) energetics and assembly of NTP-operating molecules, including proteins. PACS codes: 87.15.-v Introduction Without any exaggeration adenosinetriphosphate (ATP), Fig. 1, can be considered as the most important and fascinating molecule in living nature thanks to its ability to maintain the energy balance in living cells and initiate numerous biochemical reactions by releasing an imposing amount of energy, 7.3 ÷ 10.9 kcal/mol, which is then regained via recycling, a repeated process that occurs 2000 – 3000 times a day [1-6]. The energy is stored in the ATP triphosphate tail (TT), Fig. 1, and its release, as widely accepted, results from the ATP hydrolysis, partial (E = -7.3 kcal/ mol) or total (E = -10.9 kcal/mol) [1], accompanied by the production of adenosinediphosPublished: 4 December 2008 PMC Physics B 2008, 1:18 doi:10.1186/1754-0429-1-18 Received: 5 March 2008 Accepted: 4 December 2008 This article is available from: http://www.physmathcentral.com/1754-0429/1/18 © 2008 Tulub This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Page 1 of 13 (page number not for citation purposes) PMC Physics B 2008, 1:18 http://www.physmathcentral.com/1754-0429/1/18 phate (ADP) or adenosinemonophosphate (AMP), respectively [1,5,7]. The same is true for other known in nature nucleosidetriphosphates NTPs, N = A (adenosine), C (cytidine), G (guanosine), T (thymidine), U (uridine). In water containing environment, like living cells, ATP, and NTP in general, is quite stable, and its cleavage proceeds through overcoming a significant energy barrier of 25 kcal/mol [8-10]. The cleavage rate is highly sensitive to presence of Mg (Mg cofactor) acting on the TT as a specific catalyst [7,8]. Basically, Mg can bind to each oxygen of the TT, but generally it prefers making a chelate with O1 and O2, Fig. 1, and highly rare with O2 and O3 [1-6]. The O1-O2 chelate lowers the energy barrier by 5 kcal/mol [9,10], and the cleavage proceeds through a typical hydrolytic mechanism. What we have just outlined is a conventional view on the NTP cleavage [1-10]. The reaction path, from its initial stage and up to final, includes only ionic forms, and diphosphate NDP and monophosphate NMP products are also ionic. The ionic forms, in turn, have paired spins (singlet states) and hardly thought to be involved in rapid reactions based on the NTP cleavage. At the same time there are numerous very rapid reactions using Mg-induced NTP cleavage. Among them are tubulin assembly into microtubules (NTP = GTP) [11,12] and DNA/RNA single chain polymerization [13-16]. These reactions can be understood only through producing short-living radical Structure of ATP and Mg subsystems Figure 1 Structure of ATP and Mg subsystems. P O5