Markus Dittrich and Klaus Schulten.
PcrA helicase, a prototype ATP-driven molecular motor.
Structure, 14:1345-1353, 2006.
DITT2006
Despite extensive studies, the mechanisms underlying molecular motor
function are still poorly understood. Key to the mechanisms is
the coupling of ATP hydrolysis to conformational changes of the
motor protein. To investigate this coupling, we have conducted
quantum mechanical/molecular mechanical simulations of PcrA helicase,
a strikingly simple motor that translocates uni-directionally along
single-stranded DNA (ssDNA). Our results reveal a
close similarity in catalytic site structure and reaction pathway
to F1-ATPase including a proton relay mechanism important for efficient ATP
hydrolysis and an "arginine finger" residue being key to the coupling
of the chemical reaction to protein conformational changes.
By means of in silico mutation studies, we identified the
residue Q254 as being crucial for the coupling of ssDNA translocation
to the actual catalytic event. Based on the present result for PcrA
helicase and previous findings for F1-ATPase, we propose a general
mechanism of ATP-driven molecular motor function.
