Markus Dittrich, Shigehiko Hayashi, and Klaus Schulten.
ATP hydrolysis in the βTP and
βDP catalytic sites of F1-ATPase.
Biophysical Journal, 87:2954-2967, 2004.
(PMC: 1304769)
DITT2004
The enzyme -adenosine triphosphatase (ATPase)
is a molecular motor that converts the chemical energy stored in the molecule adenosine tri-phosphate (ATP) into mechanical rotation
of its sub-unit.
During steady state catalysis, the three catalytic sites of
operate in a cooperative fashion such that at every
instant each site is in a different conformation corresponding
to a different stage along the catalytic cycle. Notwithstanding
a large amount of biochemical and, recently, structural data
we still lack an understanding of how ATP hydrolysis in
is coupled to mechanical motion and how the
catalytic sites achieve cooperativity during rotatory catalysis.
In this publication we report combined
quantum mechanical/molecular mechanical simulations of ATP
hydrolysis in the
and
catalytic sites of -ATPase.
Our simulations reveal a dramatic change in the reaction energetics
from strongly endothermic in
to approximately
equienergetic in
.
The simulations identify the responsible protein residues, the
arginine finger R373 being the most important
one. Similar to our earlier study of
,
we find a multicenter proton relay mechanism to be the
energetically most favorable hydrolysis pathway.
The results elucidate how cooperativity between catalytic sites
might be achieved by this remarkable molecular motor.
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