TY - JOUR
T1 - PcrA Helicase, a Prototype ATP-Driven Molecular Motor
AU - Dittrich, Markus
AU - Schulten, Klaus
N1 - Funding Information:
The authors would like to thank J. Yu for fruitful discussions and for the molecular dynamics trajectories that provided the starting point for our QM/MM study. They would also like to thank T. Ha for many insights and Z. Luthey-Schulten for the great sequence-structure alignment tool in VMD. This work is supported by grants from the National Institutes of Health (PHS-5-P41-RR05969) and the National Science Foundation (NSF) (MCB02-34938). The authors gladly acknowledge computer time at the NSF centers (LRAC MCA93S028) and the Pittsburgh Supercomputer Center (NCRR Research Resource RR06009). The molecular images were created with VMD ( Humphrey et al., 1996 ).
PY - 2006/9
Y1 - 2006/9
N2 - 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 combined quantum mechanical/molecular mechanical simulations of PcrA helicase, a strikingly simple motor that translocates unidirectionally along single-stranded DNA (ssDNA). Our results reveal a close similarity in catalytic site structure and reaction pathway to those of F1-ATPase, and these similarities include a proton relay mechanism important for efficient ATP hydrolysis and an "arginine finger" residue that is 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.
AB - 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 combined quantum mechanical/molecular mechanical simulations of PcrA helicase, a strikingly simple motor that translocates unidirectionally along single-stranded DNA (ssDNA). Our results reveal a close similarity in catalytic site structure and reaction pathway to those of F1-ATPase, and these similarities include a proton relay mechanism important for efficient ATP hydrolysis and an "arginine finger" residue that is 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.
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U2 - 10.1016/j.str.2006.06.017
DO - 10.1016/j.str.2006.06.017
M3 - Article
C2 - 16962966
AN - SCOPUS:33748328253
SN - 0969-2126
VL - 14
SP - 1345
EP - 1353
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 9
ER -