The Conformon - Molecular Theory of the Living Cell - page 237

2011) who visualized the propagation of the conformational waves of the b subunits

around the isolated F 1 -ATPase stator ring (see Sect. 7.1.5 ) .
Functional (as compared to non-functional) DNA molecules carry not only
genetic information but also mechanical energy in the form of supercoils. The
mechanical energy stored in supercoiled DNA is known to be essential for tran-
scriptional activities in Escherichia coli (Benham 1996a, b), leading to the conclu-
sion that conformons are necessary for DNA functions . More recently, Ebright and
his coworkers (Revyakin et al. 2006; Kapanidis et al. 2006) provided direct
molecular dynamics evidence, obtained using a fluorescence resonance energy
transfer (FRET) technique, that conformational strain energies stored in deformed
DNA strands (called “DNA scrunching” (Cheetham and Steitz 1999)) may play a
critical role in transcription initiation in bacterial RNA polymerase. What these
authors call DNA scrunches can be identified with the conformon of Green and Ji
(1972a, b) and Ji (2000), and the SIDDs of Benham (1996a, b).

8.4 Conformons as Force Generators of Molecular Machines

It is the basic postulate of the conformon theory that all molecular machines are
driven by conformons. The sarcoplasmic/endoplasmic reticulum calcium ion pump
(i.e., the SE Ca ++ ATPase) is one of the simplest molecular machines known with a
molecular weight of 110,000 Daltons and 994 amino acid residues (Toyoshima
et al. 2000). This protein can catalyze the hydrolysis of ATP and use the free energy
of this reaction to transport two calcium ions across sarcoplasmic/endoplasmic
reticulum membranes (Myung and Jencks 1995; MacLennan and Green 2000).
The three-dimensional structure of this ion pump was determined by X-ray crystal-
lography by Toyoshima et al. (2000). Their structure is reproduced in Fig. 8.4 .
In Fig. 8.4 , the first three domains of the calcium ion pump are on the cytoplas-
mic side of the membrane and the M domain (with its ten transmembrane helixes
symbolized as M1 through M10) spans the membrane. ATP bound to the N domain
donates a phosphoryl group to aspartic residue 351 located on the P domain, across
a distance of about 25 ˚ . Two calcium ions are bound to two separate binding sites
(see the two circles side by side in the membrane domain) located in parallel
at about the mid-section of the membrane, separated by 5.7 ˚ from each other.
One of the two calcium ion-binding sites is surrounded by helixes M5, M6, and M8,
while the other site is associated mainly with helix M4. The distance between
the aspartic acid residue 351 in the N domain that is phosphorylated by ATP and the
calcium-binding sites in the M domain is estimated to be about 50 ˚ (Toyoshima
et al. 2000).
The X-ray structure of Ca ++ ATPase determined by Toyoshima et al. (2000)
provides new information that complement the dynamic properties of the pump
determined by biochemical and kinetic experiments carried out over more than four
decades since the enzyme was discovered in 1962 (Toyoshima et al. 2000;
MacLennan and Green 2000). The new X-ray structural data, combined with the