Implications of fast-time scale dynamics of human DNA/RNA cytosine methyltransferases (DNMTs) for protein function

0353911 - ÚOCHB 2011 RIV DE eng J - Článek v odborném periodiku
Evans, D. A. - Bronowska, Agnieszka Katarzyna
Implications of fast-time scale dynamics of human DNA/RNA cytosine methyltransferases (DNMTs) for protein function.
Theoretical Chemistry Accounts. Roč. 125, 3/6 (2010), s. 407-418. ISSN 1432-881X. E-ISSN 1432-2234
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: MD simulations * DNA/RNA methyltransferase * enthalpy-entropy compensation
Kód oboru RIV: CF - Fyzikální chemie a teoretická chemie
Impakt faktor: 2.903, rok: 2010

In this study, the changes in fast (picosecond-to-nanosecond time scale) dynamics of catalytic domains of four human cytosine DNA methyltransferases (DNMTs) were studied using molecular dynamics (MD) simulations. The results provide insight into the protein dynamics changes that occur upon binding of the cofactor, S-adenosylmethionine (SAM). Contrary to expectations, increased amplitude of motions of backbone amide (N–H) and terminal heavy atom (C–C) bond vectors was observed in all studied DNMTs upon binding of SAM. These results imply that the cofactor binding causes a global increase in the extent of protein dynamics in the short time scale. This global dynamic change constitutes a favourable entropic contribution to the free energy of SAM binding. These results suggest that cytosine DNA methyltransferases may exploit changes in their fast scale dynamics to reduce the entropic cost of the substrate binding.
Trvalý link: http://hdl.handle.net/11104/0193026