Effects of dimerization of Serratia marcescens endonuclease on water dynamics

Abstract

The dynamics and structure of Serratia marcescens endonuclease and its neighboring solvent are investigated by molecular dynamics (MD). Comparisons are made with structural and biochemical experiments. The dimer form is physiologic and functions more processively than the monomer. We previously found a channel formed by connected clusters of waters from the active site to the dimer interface. Here, we show that dimerization clearly changes correlations in the water structure and dynamics in the active site not seen in the monomer. Our results indicate that water at the active sites of the dimer is less affected compared with bulk solvent than in the monomer where it has much slower characteristic relaxation times. Given that water is a required participant in the reaction, this gives a clear advantage to dimerization in the absence of an apparent ability to use both active sites simultaneously.

Advantage of Being a Dimer for Serratia marcescens Endonuclease

“…Both values are smaller than 0.96 evaluated from the bulk, and β res is lower in the monomer than that in the subunit B of the dimer. Such differences clearly demonstrate that water in this area in the subunit B of the dimer is less affected by both the protein and DNA, which is the same phenomenon observed in the protein systems [20]. …”

“…The MD simulations of the free SMnase systems [20] reproduced the experimentally observed the metal coordination number and structural geometry of Mg-ligand cluster [14]. Theoretical studies of hydration properties of Mg 2+ [39,40] showed that in water it takes18.4 kcal/mol to remove one water molecule from a hexa-hydrated Mg 2+ .…”

“…Previous studies of the free protein systems [14,20] showed that Mg 2+ has an octahedral coordination with 5 water molecules and OD1 from the side chain of Asn119. The distance between Mg 2+ and each oxygen atom of the ligands is 1.97 ± 0.06 Å on average during the entire simulation, close to the value in the crystal structure which is in the range of between 2.01 and 2.13 Å [4].…”

“…We found in our previous work on the protein systems [20], the monomer and two subunits of the dimer differ in flexibility/dynamics of residues and water locally in the active site. In this work, we considered the effect of dimerization of SMnase simulation on model-built complexes of DNA with the monomer and dimer by molecular dynamics.…”

“…Also in here, N w is the total number of water molecules and T run is the length of simulation. Previous work [20] from the survival function for the hydration sites around the active site indicated that most sites were not well fit by a single exponential. We found the relaxation time behavior is better approximated with two terms using a stretched exponential for the long time decay (a Kohlraush-Williams-Watts model [33]), and a single exponential for the short time decay, $${\mathrm{normalC}}_{\alpha }\left(\mathrm{normalt}\right)={\mathrm{normalW}}_0\{(1-x)\exp [-\mathrm{t}∕{\tau }_{\mathrm{normalf}}]+x\exp [-{(\mathrm{normalt}∕{\tau }_{\mathrm{s}})}^{\beta }]\}$$ where W 0 is the occupancy of the α th site, τ f and τ s are the fast and slow residence time, respectively, x is the weight of the slow relaxation, and β is a stretching parameter between 0 and 1, which reflects the extent to which the relaxation process deviates from exponential behavior and provides us additional information upon the heterogeneity of the water dynamics around the molecule.…”