Cell Language Theory, The: Connecting Mind And Matter

The Bhopalator 77

“6x9” b2861 The Cell Language Theory: Connecting Mind and Matter

possible mechanism is suggested in Figure 3.13 that is based on the

pre-fit hypothesis rooted in the GFCP or the PSFP discussed in

Sections 2.7 and 3.2.7.

The pre-fit mechanism of the rotary catalytic activity of the F 1 -ATPase

stator ring consists of the following key steps:

(1) In the absence of ATP, the three b-subunits of the F 1 stator exist in

only one ground-state conformation designated as O (from “open”

which is equivalent to L, or the low-affinity conformation, in

Figure 3.35), and since there are three b-subunits per F 1 stator, the

ground conformational state of the F 1 stator on the whole can be

designated as (O/O/O) which is characterized by the presence of an

opening at its center (see Figure 3.12(a)). Bold red letters symbolize

the conformational state of the b-subunits and the slash indicates the

a-subunit which may also undergo conformational changes but these

changes are not detectable using the HS-AFM method employed by

Uchihashi et al. [85]. It should be noted here that the hole at the

center of the F 1 stator ring disappears when two of the three b-subunits

bind ATP and ADP (see Figure 3.12(d)) and undergo conformational

transition from the O to the C and C′ states, which are equivalent to

L or the low-affinity, M or the medium-affinity, and H or the high-

affinity conformational states, respectively, in Figure 3.35.

(2) The ground-state F 1 stator is thought to be in thermal equilibrium

with (or thermally fluctuate among) three different conformational

states designated as (O/C/C′), (C′/O/C), and (C/C′/O) (see the top

row in Figure 3.13).

(3) In the presence of ATP, the F 1 stator binds ATP to its b-subunit in the

C′ conformation, ADP (produced from ATP hydrolysis) to its b-subunit

in the C conformation, and the third b-subunit is left empty in the O

conformation.

(4) The structure of the ligand-bound F 1 stator has been selected by bio-

logical evolution because of its ability to select, out of all the theoreti-

cally possible conformational transitions, only those states that obey

the GFCP (or the PSFP).

(5) The essence of the pre-fit mechanism (in contrast to the induced-fit

mechanism of Koshland [28]) is that conformational transitions of

enzymes precede the associated ligand binding events, because the

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