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Behavior of the ATP grasp domain of biotin carboxylase monomers and dimers studied using molecular dynamics simulations
Author(s) -
Novak Brian R.,
Moldovan Dorel,
Waldrop Grover L.,
de Queiroz Marcio S.
Publication year - 2011
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22910
Subject(s) - dimer , molecular dynamics , chemistry , biotin , protein subunit , monomer , crystallography , adenosine triphosphate , atp synthase gamma subunit , atp synthase , biophysics , stereochemistry , biochemistry , enzyme , biology , atp hydrolysis , computational chemistry , atpase , organic chemistry , gene , polymer
The enzyme biotin carboxylase (BC) uses adenosine triphosphate (ATP) to carboxylate biotin and is involved in fatty acid synthesis. Structural evidence suggests that the B domain of BC undergoes a large hinge motion of ∼45° when binding and releasing substrates. Escherichia coli BC can function as a natural homodimer and as a mutant monomer. Using molecular dynamics simulations, we evaluate the free energy profile along a closure angle of the B domain of E. coli BC for three cases: a monomer without bound Mg 2 ATP, a monomer with bound Mg 2 ATP, and a homodimer with bound Mg 2 ATP in one subunit. The simulation results show that a closed state is the most probable for the monomer with or without bound Mg 2 ATP. For the dimer with Mg 2 ATP in one of its subunits, communication between the two subunits was observed. Specifically, in the dimer, the opening of the subunit without Mg 2 ATP caused the other subunit to open, and hysteresis was observed upon reclosing it. The most stable state of the dimer is one in which the B domain of both subunits is closed; however, the open state for the B domain without Mg 2 ATP is only approximately 2 k B T higher in free energy than the closed state. A simple diffusion model indicates that the mean times for opening and closing of the B domain in the monomer with and without Mg 2 ATP are much smaller than the overall reaction time, which is on the order of seconds. Proteins 2011. © 2010 Wiley‐Liss, Inc.