4.1 Functional Rotation of AcrB
67
(a)
(b)
(d)
(c)
(e)
E
B
A
E’
B’
A’
(a)
(c)
(e)
Proton binding
Structural reorganization
and
introduction of drug
Proton dissociation
Structural reorganization
and
release of drug
F P
System free energy
A
E
B
Fig. 4.3 Top: Conformational change of AcrB during one drug-transport cycle, or equivalently,
one proton-transfer cycle. A different color represents a different state (access (A), binding (B), or
extrusion (E) state). The open triangle denotes a drug molecule. (a) Start of proton-transfer cycle.
(b) Right after a proton binds to protomer B. (c) After reorganization of AcrB structure accompanied
by introduction of a drug molecule into protomer A (protomer A changes to protomer A’ upon the
reorganization). (d) Right after a proton dissociates from protomer E’. (e) After reorganization of
AcrB structure accompanied by release of a drug molecule from protomer B’ (protomer B’ changes
to protomer E upon the reorganization). End of proton-transfer cycle. The structures of AcrB in (a)
and (e) are the same. The structural changes of (a)→(b)→(c)→(d)→(e)=(a) correspond to (A, B,
E)→(A’, B’, E’)→(B, E, A). Bottom: Decrease of system free energy during one drug-transport
cycle. The net decrease is F P (<0)
The transfer of a single proton from the higher-concentration side to the lowerconcentration one leads to an increase in system entropy, and the transfer of a positive charge along the electrostatic-potential gradient results in a decrease in system
energy, which sums to a free-energy decrease of −9k B T. ξ is attributed to the pumping
of a drug molecule from the lower-concentration side to the higher-concentration one
[16]. In our view, F 1 -ATPase and AcrB share physically the same rotation mechanism.
As discussed in Sect. 2.8, the entropic insertion of a solute into a vessel consisting
of biopolymers followed by the entropic release of the solute from the vessel is a
fundamental process in a biological system. Interestingly, after a solute is inserted into
the vessel possessing a specific structure, the solute is released from the vessel upon
67
(a)
(b)
(d)
(c)
(e)
E
B
A
E’
B’
A’
(a)
(c)
(e)
Proton binding
Structural reorganization
and
introduction of drug
Proton dissociation
Structural reorganization
and
release of drug
F P
System free energy
A
E
B
Fig. 4.3 Top: Conformational change of AcrB during one drug-transport cycle, or equivalently,
one proton-transfer cycle. A different color represents a different state (access (A), binding (B), or
extrusion (E) state). The open triangle denotes a drug molecule. (a) Start of proton-transfer cycle.
(b) Right after a proton binds to protomer B. (c) After reorganization of AcrB structure accompanied
by introduction of a drug molecule into protomer A (protomer A changes to protomer A’ upon the
reorganization). (d) Right after a proton dissociates from protomer E’. (e) After reorganization of
AcrB structure accompanied by release of a drug molecule from protomer B’ (protomer B’ changes
to protomer E upon the reorganization). End of proton-transfer cycle. The structures of AcrB in (a)
and (e) are the same. The structural changes of (a)→(b)→(c)→(d)→(e)=(a) correspond to (A, B,
E)→(A’, B’, E’)→(B, E, A). Bottom: Decrease of system free energy during one drug-transport
cycle. The net decrease is F P (<0)
The transfer of a single proton from the higher-concentration side to the lowerconcentration one leads to an increase in system entropy, and the transfer of a positive charge along the electrostatic-potential gradient results in a decrease in system
energy, which sums to a free-energy decrease of −9k B T. ξ is attributed to the pumping
of a drug molecule from the lower-concentration side to the higher-concentration one
[16]. In our view, F 1 -ATPase and AcrB share physically the same rotation mechanism.
As discussed in Sect. 2.8, the entropic insertion of a solute into a vessel consisting
of biopolymers followed by the entropic release of the solute from the vessel is a
fundamental process in a biological system. Interestingly, after a solute is inserted into
the vessel possessing a specific structure, the solute is released from the vessel upon