TY - JOUR
T1 - Conformational Excitation and Nonequilibrium Transition Facilitate Enzymatic Reactions
T2 - Application to Pin1 Peptidyl-Prolyl Isomerase
AU - Mori, Toshifumi
AU - Saito, Shinji
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (JP18K05049 to T.M. and JP16H02254 to S.S.) from JSPS. The calculations are partially carried out at the Research Center for Computational Sciences in Okazaki.
PY - 2019/2/7
Y1 - 2019/2/7
N2 - Conformational flexibility of protein is essential for enzyme catalysis. Yet, how protein's conformational rearrangements and dynamics contribute to catalysis remains highly controversial. To unravel protein's role in catalysis, it is inevitable to understand the static and dynamic mechanisms simultaneously. To this end, here the Pin1-catalyzed isomerization reaction is studied from the two perspectives. The static view indicates that the hydrogen bonds involving Pin1 rearrange in a tightly coupled manner with isomerization. In sharp contrast, the isomerization dynamics are found to be very rapid; protein's slow conformational rearrangements thus cannot occur simultaneously with isomerization, and the reaction proceeds in a nonequilibrium manner. The distinctive protein conformations necessary to stabilize the transition state are prepared a priori, i.e., as conformational excited states. The present result suggests that enzymatic reaction is not a simple thermal activation from equilibrium directly to the transition state, thus adding a novel perspective to Pauling's view.
AB - Conformational flexibility of protein is essential for enzyme catalysis. Yet, how protein's conformational rearrangements and dynamics contribute to catalysis remains highly controversial. To unravel protein's role in catalysis, it is inevitable to understand the static and dynamic mechanisms simultaneously. To this end, here the Pin1-catalyzed isomerization reaction is studied from the two perspectives. The static view indicates that the hydrogen bonds involving Pin1 rearrange in a tightly coupled manner with isomerization. In sharp contrast, the isomerization dynamics are found to be very rapid; protein's slow conformational rearrangements thus cannot occur simultaneously with isomerization, and the reaction proceeds in a nonequilibrium manner. The distinctive protein conformations necessary to stabilize the transition state are prepared a priori, i.e., as conformational excited states. The present result suggests that enzymatic reaction is not a simple thermal activation from equilibrium directly to the transition state, thus adding a novel perspective to Pauling's view.
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U2 - 10.1021/acs.jpclett.8b03607
DO - 10.1021/acs.jpclett.8b03607
M3 - Article
C2 - 30607953
AN - SCOPUS:85061127804
VL - 10
SP - 474
EP - 480
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
SN - 1948-7185
IS - 3
ER -