Urry D.W. (Ed.) What Sustains Life? : Consilient Mechanisms for Protein-Based Machines and Materials

Подождите немного. Документ загружается.

8.5 The Myosin II Motor of Muscle Contraction, a Representative ATPase

445

8.5.4.7 Role of the Narrow Cleft

Emanating in Two Directions from the

ATP Binding Site to the Actin Binding Site

and to the Origin of the Powerstroke

As noted in section

8.5.4.2

and as foreseen by

Rayment and coworkers/^^'^^^ the "narrow

cleft" that "splits the 50-kDa segment" plays a

central role in the function of the myosin II

motor. In terms of the hydrophobic consiUent

mechanism, the narrow cleft becomes the struc-

tural conduit through which the force arising

from the increased thirst for hydration experi-

enced on hydrolysis of ATP to ADP plus Pi is

directed to its principal sites of action. Stereo

views that locate the nucleotide binding site at

the base of, and at a turn of, a cleft are shown

in Figure 8.58 for the near-rigor-like state in A

Cleft to actin

binding site

nucleotide

binding site

Cleft to head

of lever arm

Cleft to actin

binding site

Cleft to head

of lever arm

FIGURE 8.58. Stereo view in space-filling repre-

sentation of scallop cross-bridge (SI) showing

narrow clefts emanating in two directions from the

nucleotide binding site, located by the white circle.

One cleft runs upward to the actin binding site, and

the second direction is toward the hydrophobic asso-

ciation between the amino-terminal domain and the

head of the lever arm in A to effect the hydrophobic

dissociation of head from lever arm as shown in B.

(A) Near-rigor state. (Prepared using the crystallo-

graphic results of Himmel et al.^ as obtained from

the Protein Data Bank, Structure File 1KK7.) (B)

ATP state due to ATP analogue ADP-BeFx. (Pre-

pared using the crystallographic results of Himmel et

al.^

as obtained from the Protein Data Bank, Struc-

ture File 1KK8.)

446

8. Consilient Mechanisms for Protein-based Machines of Biology

and for the state resulting from the ATP ana-

logue, ADP-BeFx, in B. As shown in B, the

phosphate analogue is actually closer to the

opened chasm between the head of the lever

arm and the amino-terminal domain than to the

actin binding site, and it is clearly located at a

turn in the narrow cleft in order to direct its

thirst for hydration in two directions, that is,

to direct apolar-polar repulsion toward both

hydrophobic association/dissociation sites.

As argued in Chapter

on the basis of exten-

sive experimental data on elastic-contractile

model proteins, on exposure to water hydro-

phobic groups hydrate in an exothermic

reaction until too much hydrophobic hydration

forms and solubility is lost. Charged groups, of

course, dissolve in water due to the decrease in

free energy derived from hydration on passing

from the ionic interactions in a salt. In circum-

stances where hydrophobic groups and charged

groups are forced by structure to compete for

limited water, charged groups recruit emergent

hydrophobic hydration during transient hydro-

phobic dissociation so that the driving force for

hydrophobic association is lost.

The hydrophobic consilient mechanism de-

scribes this competition for hydration between

hydrophobic and charged groups as an apolar-

polar repulsive free energy of hydration, AGap,

because, when motion is available to these

groups, they reach out for water unperturbed

by the other in order to lower their respective

free energies of hydration. Thus, the competi-

tion for water is seen as a repulsion between

charged and hydrophobic groups, as these

groups attempt to distance themselves from

each other in order to access water unper-

turbed by the other.

The occupancy state for a nucleotide binding

site with the greatest thirst for water, and hence

with the greatest repulsion between charged

and hydrophobic groups, would be

ADP^"

Mg^^

HPOl". Formation of this occupancy state

would most dramatically drive the structural

transition observed on going from the near-

rigor state to the ATP analogue state that

rep-

resented in the preceding series of figures. The

most effective way to direct the thirst for hydra-

tion is by means of the narrow clefts noted in

Figures 8.58 and 8.59. Thus, we beUeve AGap to

be the decisive force in the function of the

myosin II motor.

8.5.5 The Hydrophobic ConsiUent

Mechanism's Integration of the

Calcium Ion Trigger into the

Contraction/Relaxation Cycle

8,5.5.1 Putting the Near-rigor and ATP

Analogue States of Scallop Muscle

in Perspective

8.5.5.1.1

Correlation of the Consilient

Mechanisms with Differences Between the

Near-rigor and ATP Analogue States of

Scallop Muscle

In Figures 8.47 through 8.58, two states of the

myosin II motor are compared using specific

reference conditions. In our view, these two

states differ most dramatically by their extents

of hydrophobic association. Clearly, the state

with less polar occupancy of the nucleotide

binding site favors greater hydrophobic associ-

ation, and the state with more polar occupancy

of the nucleotide binding site favors hydropho-

bic dissociation. The differences between the

two states become explicable in terms of the

hydrophobic and elastic consilient mechanisms,

and the difference between the two states pro-

vides for displacement of the sort required for

the motion of muscle contraction.

8.5.5.1.2

The Two States Truly Represent

Neither the Desired Least Polar, Unoccupied

Binding Site Nor the Most Polar State with

ADP^-

Mg^^ HPO/- in the Nucleotide

Binding Site

The near-rigor state contains the polar magne-

sium sulfate salt, S04^" Mg^^, and, even though

the charges of the magnesium sulfate ion pair

sum to a net zero charge, as regards thirst for

hydration, the polarity of the sulfate would be

reduced to no more than

one-half.

Because of

this,

the analyzed near-rigor state should not

be assumed to exhibit the maximal hydropho-

bic association of an unoccupied nucleotide

binding site. Also, the ATP analogue state

achieved on occupancy by ADP^" Mg^^ BeFs^"

would not be as polar as the state with ADP^"

!.5 The Myosin II Motor of Muscle Contraction, a Representative ATPase 447

Cleft to actin binding site under overhang

Cleft to head

of lever arm

FIGURE 8.59. Stereo view in space

filling

representa-

tion of scallop muscle cross-bridge (SI) looking

along the lever arm (lower left) from the foot to the

nucleotide binding site that contains the ATP ana-

logue ADP-BeFx and showing continuity of narrow

clefts from the binding site in both directions—to the

actin binding site from center to upward left and to

effect hydrophobic dissociation of the head of lever

arm from under the amino-terminal domain. (Pre-

pared using the crystallographic results of Himmel et

al.^

as obtained from the Protein Data Bank, Struc-

ture File 1KK8.)

Mg^^ HPO4 occupying the nucleotide binding

site.

Accordingly, this ATP analogue state may

not convert the cross-bridge intramolecularly

to a completely hydrophobically dissociated

state.

Thus, one should not be surprised to find

states at even more extremes of hydrophobic

dissociation and of hydrophobic association

occurring in the myosin II motor. Nonetheless,

this important work of Himmel et al.^ demon-

strates changes that, in our view, remarkably

substantiate the hydrophobic elastic consilient

mechanism. On the basis of the hydrophobic

consilient mechanism and especially its compo-

nent apolar-polar repulsive free energy of

hydration, AGap, these two structures provide

the opportunity with which to introduce the

calcium ion trigger into the contraction/relax-

ation cycle.

5.5.5.2

Hydrophobic Consilient

Mechanism Whereby Calcium Ion Can

Trigger the Powerstroke

8.5.5.2.1

Calcium Ion Binding Displaces

Tropomyosin to Open the Tight Binding Site

on Actin for Hydrophobic Association with

the Myosin Cross-bridge

The excitatory nerve impulse stimulates release

of calcium from the sarcoplasmic reticulum.

The calcium ion then binds to carboxylates of

troponin C in an otherwise hydrophobic region

located on the actin filament. This creates a

new site for hydrophobic association that

brings about the relocation of tropomyosin

from its actin site of hydrophobic association to

a new hydrophobic site associated with the

448

8. Consilient Mechanisms for Protein-based Machines of Biology

actin filament. By relocation of tropomyosin,

the tight binding site opens up on actin for

hydrophobic association of the myosin cross-

bridge. The association is expected to involve

particularly complimentary actin and myosin

surfaces with expression of high hydrophobic-

ity due to reduction of polarity by well-

positioned ion pairing between surfaces involv-

ing negative carboxylates and positively

charged amino acid side chains, as discussed in

relation to Figure 8.2.

8.5.5.2.2. Proximity of Hydrophobic Binding

Site on Actin to the Nucleotide Binding Site

of the Myosin Head Displaces Phosphate by

Apolar-Polar Repulsion

This increase in hydrophobicity presented by

the actin component of the complementary

myosin-actin binding site directs an apolar-

polar repulsion through the conduit of the

narrow cleft to assist in expelling the phos-

phate. More simply stated, cross-bridge binding

to the tight site on actin limits access of ADP

plus Pi to hydration, and thereby raises the free

energy of ADP plus Pj at the nucleotide-

binding site with the result of the release of Pi.

8.5.5.2.3

Expulsion of Phosphate Sets Off

Hydrophobic Association of the Head of the

Lever Arm with the Amino-terminal Domain

to Give the Powerstroke

The expulsion of phosphate removes the

apolar-polar repulsion holding open the

aqueous chasm between the head of the lever

arm and the amino-terminal domain to result in

the powerstroke. Then ADP releases more

slowly, because ADP is repulsed to a lesser

extent than phosphate and because ADP does

not fit the nucleotide binding site as well as it

fits

ATP.

8.5,5,3 ATP Binding and the State of ATP

in Detached Cross-bridges

8.5.5.3.1

ATP Binding Releases Cross-bridge

Attachment to the Actin Filament

With the empty nucleotide binding site being

exactly configured for occupancy by the ATP

molecule,^^"^ ATP occupies the nucleotide

binding site with a greater affinity than ADP.

In doing so, the polar ATP molecule introduces

an apolar-polar repulsion directed at the actin

binding site and thereby effects detachment of

the cross-bridge from the actin filament. Now,

further insight into the contraction/relaxation

cycle comes from knowing the enzymatic activ-

ity within the nucleotide binding site of the

detached state.

8.5.5.3.2

The State of the Nucleotide in the

Detached Cross-bridge

First we note that as few as 2% of the cross-

bridges are attached to the actin filament at

any one time.^^^ This being the case, it becomes

central to the mechanism to know the situation

within the nucleotide binding site of the 98% of

cross-bridges that are detached.^^^ As described

over three decades ago by Lymn and Taylor,^^^

"actin binds with the myosin ADP P complex

and displaces products of the hydrolysis reac-

tion. It is concluded that this step is responsible

for activation of myosin ATPase by actin." With

98%

of the cross-bridges detached and with the

rapid conversion of ATP to ADP + Pi (often

noted as ADP

P),^^^

the most polar state of

the cross-bridge would be the one readied

for hydrophobic association with the com-

plementary tropomyosin-vacated, hydrophobic

binding site on actin, which could provide an

apolar-polar boost for repulsion of phosphate

from the cross-bridge.

Thereby, the hydrophobic consilient mecha-

nism integrates the calcium ion trigger into the

contraction/relaxation of the myosin II motor

as well as provides the physical basis for the

powerstroke.

References

E.O.Wilson, Consilience: The Unity of Knowl-

edge. Alfred E.

Knopf,

New York, 1998, p. 8.

C. Lange and C. Hunte, "Crystal structure of the

yeast cytochrome bci complex with its bound

substrate cytochrome c." Proc. Nat.

Acad.

Sci.

USA,

99, 2800-2805,2002.

D.M. Himmel,

Gourinath, L Reshetnikova, Y.

Shen, A.G. Szent-Gyorgyi, and C. Cohen, "Crys-

tallographic Findings on the Internally Uncou-

References 449

pled and Near-rigor States of Myosin: Further

Insights into the Mechanics of the Motor."

Proc. Natl

Acad.

ScL U.S.A., 99, 12645-12650,

2002.

A.J. Fisher, C.A. Smith, J. Thoden, R. Smith, K.

Sutoh, H.M. Holden, and I. Rayment, "Struc-

tural Studies of MyosinrNucleotide Complexes:

A Revised Model for the Molecular Basis of

Muscle Contraction." Biophys. /., 68, 19s-28s,

1995.

J. Monod, "On Symmetry and Function in Bio-

logical Systems." In Nobel Symposium

11:

Sym-

metry and Function of Biological Systems at the

Macromolecular Level, A. Engstrom and B.

Strandberg, Eds., Almqvist & Wiksell Forlag

AB,

Stockholm, 1968, p. 1527. Also reprinted

in Selected Papers in Molecular Biology by

Jacques

Monod,

Lwoff and A. Ullmann, Eds.,

Academic Press, New York, 1978, p. 708.

6. M.F. Perutz, "Mechanisms of Cooperativity and

Allosteric Regulation in Proteins." Q. Rev.

Biophys., 22,139-236,1989.

M.F. Perutz, Mechanisms of Cooperativity and

Allosteric Regulation in Proteins. Cambridge

University Press, Cambridge, 1990, page ••.

8. D.W. Urry and T.M. Parker, "Mechanics of

Elastin: Molecular Mechanism of Biological

Elasticity and its Relevance to Contraction." /.

Muscle Res. Cell Motility, 23, 541-547, 2002.

9. J.T. Edsall, "Apparent Molal Heat Capacities of

Amino Acids and Other Organic Compounds."

J. Am. Chem. Soc, 57,1506-1507,1935.

10.

J.A.V. Butler, "The Energy and Entropy of

Hydration of Organic Compounds." Trans.

Faraday Soc, 33, 229-238,1937.

11.

Two curiously complementary and impeding

truisms face any newly proposed concept or

outlook in science. They are demonstrable by

two quotations. The first, attributed to Maurice

Maeterhnck, indicates the struggle faced by

those who would make new proposals, "At

every crossway on the road that leads to the

future, tradition has placed against each of us,

10,000 men to guard the past." The second sug-

gests why it is so easy for those holding with tra-

dition, "Keep in mind that new ideas are

commonplace, and almost always wrong'' (E.O.

Wilson, Consilience: The Unity of Knowledge,

1998).

Accordingly, we have the corollary that

to stand against a new idea is to be almost

always right, with neither understanding nor

thought required. This provides an irresistible

opportunity for the more pretentious, but less

so in the realm of scientific inquiry than in the

machinations of society at large.

Then there is another aspect, noted by

Francis Bacon in The New Organon: "The

human understanding is no dry light, but

receives an infusion from the will and affec-

tions;

whence proceed sciences which may be

called 'sciences as one would wish.' For what a

man had rather were true he readily believes."

Clearly, it is particularly difficult for anyone to

allow even partial marginalization of a hard-

won and once thoroughly empowering view-

point. Of course, the basic test of any point of

view remains the extent to which it leads to

gains in further understanding of the laws of

nature.

In fact, the most satisfying aspect of scientific

pursuit is that there is a correct and unchang-

ing truth and that progress is most assured by

hewing to the path of truth as closely as

humanly possible. As reported in part in

Chapter 5, the sequential de novo design of one

class of protein-based machines after another

and the immediately successful test of each

design for its intended new energy conversion

ensures the fundamental correctness of the

hydrophobic consilient mechanism, now most

directly described in technical terms as the

comprehensive hydrophobic effect and its

operative component, the apolar-polar repul-

sive free energy of hydration. Within polymers

changes in hydrophobic association often

couple to changes in elastic force.

12.

Tb and Tt are different experimental measure-

ments of the onset temperature for the transi-

tion to hydrophobic association that have been

referenced by extrapolation to a common state

of (GXGVP)n, as shown in Figure 5.9B and

described in section 5.3.2, where X is any of the

naturally occurring amino acid residues or a

chemical modification

thereof.

As shown in

Figure 5.1, Tt is the onset temperature for

aggregation, as followed by light scattering, and

Tb is the onset temperature for the transition

for hydrophobic association, as obtained from

calorimetry data of the inverse temperature

transition. The bold-faced quantities represent

the extrapolated reference values whereas the

non-bold-faced quantities, Tb and Tt, represent

the experimentally measured quantity on

the particular composition of protein-based

polymer. For the basic homopolypentapeptide,

(GVGVP)n the bold-faced and non-bold-faced

quantities are the same.

13.

These approximations derive from the finite

width of the inverse temperature transition,

that is, from the substantial temperature inter-

450

8. Consilient Mechanisms for Protein-based Machines of Biology

val of the cusp of insolubiUty in Figure 7.1.

Should the width of the transition be one

degree or less, then the equahties would essen-

tially be exact.

14.

M.V. Stackelberg and H.R. MuUer, "Zur Struk-

tur der Gashydrate." Naturwissenschaften, 38,

456,1951.

15.

Personal communication from J. Carlos

Rodriguez-Cabello, Dpto. Fisica de la

Materia Condensada, E.T.S.I.I., Universidad de

ValladoHd, Spain,

2003.

16.

J.C. Rodriguez-Cabello, J. Reguera, M. Alonso,

T.M. Parker, D.T. McPherson, and D.W. Urry,

"Endothermic and Exothermic Components of

an Inverse Temperature Transition for Hydro-

phobic Association by TMDSC." Chem. Phys.

Lert, 388,127-131,2004.

17.

J.E. Lennard-Jones, "The Equation of State of

Gases and Critical Phenomena." Physica, 4,

941-956,1937.

18.

R.A. Buckingham, "The Classical Equation of

State of Gaseous Helium, Neon and Argon."

Proa R. Soc. A, 168, 264-283,1938.

19.

As noted in the opening paragraph of the Pro-

logue and in the initial paragraphs of Chapter

Thales of Miletus launched scientific investi-

gation in the sixth century

with the inquiry

"What is the world made of?" His simple

answer of "water" gave rise to subsequent deri-

sion. As his reasoning seems to have been

"perhaps from seeing that the nutriment of all

things is moist and kept alive by it,"^° we believe

Thales to have been essentially correct as

regards function of living things. In recognition

of Thales' initiation of our quest and because of

the central role that water fills (by the consilient

mechanisms) in function of the protein-based

machines that sustain Life, we refer to this key

water as the waters of Thales.

20.

D.J. Boorstin, The Seekers: The Story of Man's

Continuing Quest to Understand His

World.

Random House, New York, 1998, p. 22.

21.

PL. Privalov, "Cold Inactivation of Enzymes."

Crit. Rev. Biochem. Mol Biol, 25, 281-305,

1990.

22.

D.W. Urry, M.M. Long, and H. Sugano, "Cyclic

Analog of Elastin Polyhexapeptide Exhibits an

Inverse Temperature Transition Leading to

Crystallization." /. Biol. Chem. 253, 6301-6302,

1978.

23.

G. Lenaz, "A Critical Appraisal of the Mito-

chondrial Coenzyme Q Pool." FEBS Lett, 509,

151-155,

2001.

24.

C. Hunte, "Insights from the Structure of the

Yeast Cytochromes bci Complex: Crystalliza-

tion of Membrane Proteins with Antibody

Fragments." FEBS Lett, 504,126-132, 2001.

25.

C. Hunte, J. Koepke, C. Lange, T. Rossmanith,

and H. Michel, "Structure at 2.3 A Resolution

of Cytochrome bci Complex from the Yeast

Saccaromyces cerevisiae Co-crystallized with an

Antibody Fv Fagment." Structure, 8, 669-684,

2000.

26.

D.W. Urry, "Five Axioms for the Functional

Design of Peptide-Based Polymers as Mole-

cular Machines and Materials: Principle for

Macromolecular Assemblies." Biopolymers

(Peptide Science), 47, 167-178,1998.

27.

D.W. Urry, L.C. Hayes, D.C. Gowda, S.-Q. Peng,

and N. Jing, "Electro-chemical Transduction

in Elastic Protein-based Polymers." Biochem.

Biophys. Res. Commun., 210,1031-1039,1995.

28.

L. Hayes, "Effect of Hydrophobicity of Elastic

Protein-based Polymers on Redox Potential."

Ph.D.

Dissertation, The University of Alabama

at Birmingham, 1998.

29.

M.A. Khaled, V. Renugopalakrishnan, and

D.W. Urry, "Proton Magnetic Resonance and

Conformational Energy Calculations of Repeat

Peptides of Tropoelastin: The Tetrapeptide."

/. Am. Chem. Soc, 98,7547-7553,1976.

30.

V. Renugopalakrishnan, M.A. Khaled, and

D.W. Urry, "Proton Magnetic Resonance and

Conformational Energy Calculations of Repeat

Peptides of Tropoelastin: The Pentapeptide."

/. Chem. Soc, Perkin II, 111-119,1978.

31.

D.W. Urry, S.-Q. Peng, D.C. Gowda, T.M.

Parker, and R.D. Harris, "Comparison of Elec-

trostatic- and Hydrophobic-induced pKa Shifts

in Polypentapeptides: The Lysine Residue."

Chem.

Phys. Lett, 225, 97-103,1994.

32.

D.W. Urry, S.-Q. Peng, and T.M. Parker, "Delin-

eation of Electrostatic- and Hydrophobic-

induced pKa Shifts in Polypentapeptides: The

Glutamic Acid Residue." /. Am. Chem. Soc,

115,

7509-7510,1993.

33.

R. Buchet, C.-H. Luan, K.U. Prasad, R.D.

Harris, and D.W. Urry, "Dielectric Relaxation

Studies on Analogs of the Polypentapeptide of

Elastin." /. Phys. Chem. 92, 511-517,1988.

34.

WP. Jencks, "Free Energies of Hydrolysis and

Decarboxylation." In Handbook of Biochem-

istry and Molecular Biology, Third Edition,

G.D. Fasman, Ed., Physical and Chemical Data,

Vol. I, CRC Press, Boca Raton, FL, 1976, pp.

296-304.

References 451

35.

H.M. Kalckar, "The Nature of Energetic Cou-

pling in Biological Synthesis." Chem. Rev., 28,

71-142,1941.

36.

T.L. Hill and M.H. Morales, "On 'High Energy

Phosphate Bonds' of Biochemical Interest." /.

Am.

Chem. Soc., 73,1656-1660,1951.

37.

A. Pullman and B. Pullman, Quantum Bio-

chemistry, Interscience, New York, 1963.

38.

D.B. Boyd and W.N Lipscomb, "Electronic

Structures for Energy-rich Phosphates." /.

Theor. Biol., 25,403-420,1969.

39.

P George, R.J. Witonsky, M. Trachtman, C. Wu,

W. Dorwart, L. Richman, W. Richman, F.

Shurayh, and B. Lentz, "'Squiggle-H20' An

Enquiry into the Importance of Solvation

Effects in Phosphate Ester and Anhydride

Reactions." Biochim. Biophys. Acta, 223, 1-15,

1970.

40.

M.D. Hayes, L.G. Kenyon, and PA. Kollman,

"Theoretical Calculations of the Hydrolysis

Energies of Some 'High Energy' Molecules. 2.

A Survey of Some Biologically Important

Hydrolytic Reactions." /. Chem. Soc, 100,

4331-4340,1978.

41.

L. de Meis, "Role of Water in the Energy of

Hydrolysis of Phosphate Compounds—Energy

Transduction in Biological Membranes."

Biochim. Biophys. Acta, 973, 333-349,1989.

42.

C.S. Ewig and J.R. Van Wazer, "Ab Initio Struc-

trures of Phosphoric Acids and Ester.

The P-

O-P Bridged Compounds H4P202n-i for n = 1 to

4."

Am. Chem. Soc, 110, 79-86,1988.

43.

R. Cross, "Introduction: The Mechano-

biochemistry of Molecular Motors." Essays

Biochem. Mol. Motors, 35,1-2, 2000.

44.

G. Oster and H. Wang, "How Protein Motors

Convert Chemical Energy into Mechanical

Work." In Molecular Motors, M. Schhwa, Ed.,

Wiley-VCH GmbH and Co. KgaA, Weinheim,

2003,

pp. 207-227.

45.

Two excellent and current biochemistry texts

may be sought for more background and

additional detail: D. Voet, J.G. Voet, and C.W

Pratt, Fundamentals of Biochemistry, John

Wiley & Sons, Inc., New York, 1999, and Berg

et al.''

46.

J.M. Berg, J.L. Tymoczko, and L. Stryer, Bio-

chemistry, Fifth Edition, W.H. Freeman and

Company, New York, 2002.

47.

D. Voet and J.G. Voet, Biochemistry, Second

Edition, John Wiley & Sons, 1995, p. 587.

48.

M. Saraste, "Oxidative Phosphorylation as the

fin de siecle.'' Science, 283,1488-1493,1999.

49.

B.E. Schultz and S.I. Chan, "Structures and

Proton-pumping Strategies of Mitochondrial

Respiratory Enzymes." Annu. Rev. Biophys.

Biomol. Struct, 30, 23-65, 2001.

50.

P. Mitchell, "Keilin's Respiratory Chain

Concept and its Chemiosmotic Consequences."

Science, 206,1148-1159,1979.

51.

T.L. Hill and E. Eisenberg, "Can Free Energy

Transduction be Localized at Some Crucial

Part of the Enzymatic Cycle?" Quart. Rev.

Biophys., 14,463-511,1981.

52.

Grigorieff,

"Three-dimensional Structure of

Bovine NADH:Ubiquinone Oxidoreductase

(Complex I) at

A in Ice." / Mol Biol, 111,

1033-1048,1998.

53.

B. Bottcher, D. Scheide, M. Hasterberg, L.

Nagel-Stegerand, and T. Friedrich, "A Novel,

Enzymatically Active Conformation of the

Escherichia coli NADH:Ubiquinone Oxidore-

ductase (Complex I)." /. Biol. Chem., Ill,

11910-11911,

2002.

54.

V. Yankovskaya, R. Horsefield, S. Tornroth, C.

Luna-Chavez, H. Miyoshi, C. Leger, B. Byrne,

G. Cecchini, and S. Iwata, "Architecture of Suc-

cinate Dehydrogenase and Reactive Oxygen

Species Generation." Science, 299, 700-704,

2003.

55.

C.R.D. Lancaster, A. Kroger, M. Auer, and

H. Michel, "Structure of Fumarate Reductase

from Wolinella succinogenes at 2.2 A resolu-

tion." Nature, 402, 377-385,1999.

56.

D. Xia, C.A. Yu, H. Kim, J.Z. Xia, A.M.

Kachurin, L. Zhang, L. Yu, and J. Deisenhofer,

"Crystal of the Cytochrome bci Complex from

Bovine Heart Mitochondria." Science, 277,

60-66,1997.

57.

Z. Zhang, L. Huang, V.M. Shulmeister, Y.I. Chi,

K.K. Kim, L.W. Hung, A.R. Crofts, E.A. Berry,

and S.H. Kim, "Electron Transfer by Domain

Movement in Cytochrome bci." Nature, 392,

677-684,1998.

58.

S. Iwata, J.W. Lee, K. Okada, J.K. Lee, M. Iwata,

Rasmussen, T.A. Link, S. Ramaswamy, and

B.K. Jap, "Complete Structure of the 11-Sub-

unit Bovine Mitochondrial Cytochrome bci

Complex." Science, 281, 64-71,1998.

59.

C. Lange and C. Hunte, "Crystal Structure of

the Yeast Cytochrome bci Complex with its

Bound Substrate Cytochrome c." Proc. Natl

Acad.

ScL

U.S.A.,

99,2800-2805, 2002.

60.

A.R. Crofts, V.P. Shinkarev, S.A. Dikanov, R.I.

Samoilova, and D. Kolling, "Interactions of

Quinone with Iron-sulfur Protein of the bci

452

8. Consilient Mechanisms for Protein-based Machines of Biology

Complex: Is the Mechanism Spring-loaded?"

Biochim. Biophys. Acta, 1555,48-53,2002.

61.

D.W. Urry, R.D. Harris, and K.U. Prasad,

"Chemical Potential Driven Contraction and

Relaxation by Ionic Strength Modulation of an

Inverse Temperature Transition," /. Am. Chem.

Soc, 110, 3303-3305,1988.

62.

D.W. Urry, B. Haynes, H. Zhang, R.D. Harris,

and K.U. Prasad, "Mechanochemical Coupling

in Synthetic Polypeptides by Modulation of an

Inverse Temperature Transition." Proc. Natl

Acad.

Sci. U.S.A., 85, 3407-3411,1988.

63.

T. Tsukihara, H. Aoyama, E. Yamashita, T

Tomizaki, H. Yamaguchi, K. Shinzawa-Itoh,

R. Nakashima, R. Yaono, and S. Yoshikawa,

"Structures of Metal Sites of Oxidized Bovine

Heart Cytochrome c Oxidase at

2.8

A." Science,

269,1069-1074,1995.

64.

T. Tsukihara, H. Aoyama, E. Yamashita, T.

Tomizaki, H. Yamaguchi, K. Shinzawa-Itoh, R.

Nakashima, R. Yaono, and S. Yoshikawa, "The

Whole Structure of the 13-Subunit Oxidixed

Cytochrome c Oxidase at

2.8

A." Science, 272,

1136-1144,1996.

65.

J.A. Garcia-Horsman, B. Barquera, J. Rumbly,

J. Ma, and R.B. Gennis, "The Superfamily of

Heme-copper Respiratory Oxidases." /. Bacte-

riol, 176, 5587-5600,1994.

66.

Abramson,

Riistama, G. Larsson, A. Jasiatis,

M. Svensson-Ek, L. Laakkonen, A. Puustinen,

S. Iwata, and M. Wikstrom, "The Structure of

the Ubiquinol Oxidase from E. coli and its

Ubiquinone Binding Site." Nature Struct. Biol,

910-917,2000.

67.

S. Yoshikawa, K. Shinzawa-Itoh, R.

Nakashima, R. Yaono, E. Yamashita, N. Inoue,

M. Yao, M.J. Pel, C.P Libeu, T, Mizushima, H.

Yamaguchi, T. Tomizaki, and T Tsukihara,

"Redox-coupled Crystal Structural Changes in

Bovine Heart Cytochrome c Oxidase." Science,

280,1723-1729,1998.

68.

M. Wikstrom and M.I. Verkhovsky, "Proton

Translocation by Cytochrome c Oxidase in

Dif-

ferent Phases of the Catalytic Cycle." Biochim.

Biophys. Acta, 1555,128-132,2002.

69.

M. Wikstrom, "Mechanism of Proton Translo-

cation by Cytochrome c Oxidase: A New Four-

stroke Histidine Cycle." Biochim. Biophys.

Acta, 1458,188-198,2000.

70.

M. Svensson-Ek, J. Abramson, G. Larsson, S.

Tornroth, P Brzezinski, and S. Iwata, "The X-

ray Crystal Structures of Wild-type and EQ

(1-286) Mutant Cytochrome c Oxidases from

Rhodobacter sphaeroides. J. Mol. Biol, 321,

329-339, 2002.

71.

R. Mitchell, P Mitchell, and PR. Rich,

"Protonation of the Catalytic Intermediates

of Cytochrome c Oxidase." Biochim. Biophys.

Acta, 1101,188-191,1992.

72.

R. Mitchell and PR. Rich, "Proton Uptake by

Cytochrome c Oxidase on Reduction and on

Ligand Binding." Biochim. Biophys. Acta, 1186,

19-26,1994.

73.

N. Capitanio, TV. Vygodina, G. Capitanio,

A.K. Konstantinov, P. Nichols, and S. Papa,

"Redox-Linked Proteolytic Reactions in

Soluble Cytochrome-c Oxidase from Beef

Heart Mitochondria: Redox Bohr Effects."

Biochim. Biophys. Acta, 1318, 255-265,

1997.

74.

D.W. Urry and H. Eyring, "Optical Rotatory

Disperson Studies of L-Histidine Chelation." /.

Am.

Chem. Soc, 86,4574-4580,1964.

75.

Could the CUA center function in a manner

equivalent to the Qo site of Complex III? Con-

siderations: (1) The

CUA

center receives elec-

trons from cytochrome c. (2) There are quinol

oxidase enzymes that have the heme-heme-

copper dioxygen reduction site but not the

CUA

center, that is, the

CUA

center would seem to

replace the quinol oxidation site—the Qo site.

(3) Comparison of the oxidized and reduced

states of cytochrome c oxidase show that the

singular substantial conformational change

includes histidine (H204) coordinating the

CUA

center. (4) The coordination geometry of the

CUA

center showed reduction to shift from

mixed valence to the fully reduced form and a

small increase in Cu-Cu distance (2.43 to

2.51

A). This, we suggest, could correlate on

subsequent oxidation with the release of a

proton from H204. (5) The proton uptake by

cytochrome c oxidase on reduction and on

ligand binding^^: Where 2 of 2.4 protons taken

up on reduction were assigned to the binuclear

center, the remaining fraction had the heme

a/CuA. Possible problem: the

CUA

center was not

within the lipid layer, and there was no obvious

obligatory source of protons from within the

lipid layer except perhaps by means of the D-

channel.

76.

K. Kinosita, R. Yasuda, and H. Noji, "Fi-

ATPase: A Highly Efficient Rotary ATP

Machine." Essays Biochem. Mol Motors, 35,

3-18,2000.

77.

R.I. Menz, J.E. Walker, and A.G.W LesUe,

"Structure of Bovine Mitochondrial Fi-ATPase

with Nucleotide Bound to All Three Catalytic

Sites:

Implications for Mechanism of Rotary

Catalysis." Cell, 106,

331-341,

2001.

References

453

78.

R.H. Fillingame, "Molecular Rotary Motors."

Science, 286,1687-1688,1999.

79.

P.L. Pedersen, Y.H. Ko, and S. Hong, "ATP Syn-

thases in the Year 2000: Evolving Views about

the Structures of These Remarkable Enzyme

Complexes." /. Bioenerget. Biomembranes, 32,

325-332, 2000.

80.

R.H. Fillingame, CM. Angevine, and O.Y.

Dmitriev, "Coupling Proton Movements to c-

Ring Rotation in FIFO ATP Synthase: Aqueous

Access Channels and Helix Rotations at the

a-c Interface." Biochim. Biophys. Acta, 1555,

29-36,

2002.

81.

A. Horak, H. Horak, and M. Packer, "Subunit

Composition and Cold Stabihty of the

Pea Cotyledon Mitochondrial Fl-ATPase."

Biochim. Biophys. Acta, 893,190-196,1987.

82.

M.E. Pullman, H.S. Penefsky, A. Datta, and E.

Racker, "Partial Resolution of the Enzymes

Catalyzing Oxidative Phosphorylation. I. Purifi-

cation and Properties of Soluble, Dinitrophe-

nol-stimulated Adenosine Triphosphatase." /.

Biol. Chem., 235, 3322-3329,1960.

83.

D. Stock, A.G.W. Leslie, and J.E. Walker, "Mol-

ecular Architecture of the Rotary Motor in

ATP Synthase." Science, 286,1700-1705,1999.

84.

J.P Abrahams, A.G.W. LesHe, R. Lutter, and J.E.

Walker, "Structure at 2.8 A of Fi-ATPase from

Bovine Heart Mitochondria." Nature (Lond.),

370,

621-628,1994.

85.

P.B. Boyer, "New Insights into One of Nature's

Remarkable Catalysts, the ATP Synthase." Mol.

Cell Prev., 8,246-247,2001.

86.

P.D. Boyer, "The Binding Change Mechanism

for ATP Synthase—Some Probabilities and

Possibihties." Biochim. Biophys. Acta, 1140,

215-250,1993.

87.

PD. Boyer, "The ATP Synthase—A Splendid

Molecular Machine." ^n«w. Rev. Biochem., 66,

717-749,1997.

88.

L. Pauling, "The Energy of Single Bonds and

the Relative Electonegativities of Atoms."/.

Am.

Chem. Soc, 54, 3570-3582,1932.

89.

L. Pauling, The Nature of the Chemical Bond

and the Structure of Molecules and Crystals: An

Introduction to Modern Structural Chemistry,

Third Edition, Cornell University Press, Ithaca,

New York, 1960, p. 93.

90.

R.I. Menz, A.G. LesHe, and J.E. Walker, "The

Structure and Nucleotide Occupancy of Bovine

Mitochondrial Fi-ATPase are not Influenced

by Crystallization at High Concentrations of

Nucleotide." FEBS Lett., 494,11-14, 2001.

91.

K. Braig, R.I. Menz, M.G. Montgomery, A.G.W.

Leshe, and J.E. Walker, "Structure of Bovine

Mitochondrial Fi-ATPase Inhibited by Mg(2+)

ADP and Aluminum Fluoride." Structure

(Lond.),

8, 567-573, 2000.

92.

E. Cabezon, M.G. Montgomery, A.G.W. Leslie,

and J.E. Walker, "The Structure of Bovine

Mitochondrial Fi-ATPase in Complex with its

Regulatory Protein If

1."

Nature Struct. Biol., 10,

744-750.

93.

H. Noji, R. Yasuda, M. Yoshida and K. Kinosita,

"Direct Observation of the Rotation of

Fi-ATPase." Nature (Lond.), 386, 299-302,

1997.

94.

H. Noji, "Amersham Pharmacia Biotech &

Science Prize: The Rotary Enzyme of the Cell:

The Rotation of Fi-ATPase." Science, 282,

1844-1845,1998.

95.

K. Kinosita Jr., R. Yasuda, H. Noji, and K.

Adachi, "A Rotary Motor that can Work at

Near 100% Efficiency" Philos. Trans. R. Soc.

Lond.

B, 355, 473-489,2000.

96.

Borland's Illustrated Medical Dictionary, 27th

Edition, WB. Saunders, 1985, p. 1468.

97.

D. Voet, J.G. Voet & C.W Pratt, Fundamentals

of Biochemistry, John Wiley & Sons, New York,

1999,

Figures 7-22 and 7-23, p. 181.

98.

D. Voet and J.G. Voet, Biochemistry, Second

Edition, John Wiley & Sons,

1995,

Figure 34-65,

1247, and 34-67, p. 1249.

99.

A.F. Huxley and R. Niedergerke, "Interference

Microscopy of Living Muscle Fibers." Nature,

173,

971-973,1954.

100.

A.F. Huxley, "Muscle Structure and Theories of

Contraction." Prog. Biophys. Biophys. Chem., 7,

255-318,1957.

101.

D. Voet, J.G. Voet, and C.W. Pratt, Fundamen-

tals of Biochemistry, John Wiley & Sons, New

York, 1999, Figure 7-29, p. 183.

102.

I. Rayment, WR. Rypniewski, K. Schmidt-Base,

R. Smith, D.R. Tomchick, M.M. Benning, D.A.

Winkelman, G. Wesenberg, and H.M. Holden,

"Three-Dimensional Structure of Myosin Sub-

fragment-1:

A Molecular Motor." Science, 261,

50-58,1993.

103.

I. Rayment, H.M. Holden, M. Whittaker, CB.

Yohn, M. Lorenz, K.C. Holmes, and R.A.

Milligan, "Structure of the Actin-Myosin

Complex and its Implications for Muscle Con-

traction." Science, 261, 58-65,1993.

104.

I. Rayment, C. Smith, and R.G Yount, "The

Active Site of Myosin." Annu. Rev. Physiol.,

5H,

671-702,1996.

105.

Y. Lecarpentier, D. Chemla, J.C. Pourny, and

F.-X. Blanc, "Myosin Cross Bridges in Skeletal

Muscles: 'Rower' Molecular Motors." /. Appl.

Physiol., 91, 2479-2486, 2001.

454

8. Consilient Mechanisms for Protein-based Machines of Biology

106.

One might raise the issue of whether the 98%

of detached cross-bridges and the arrangement

of the tropomyosin-troponin (T-C-I) complex

on actin might influence availability of troponin

C to the released calcium ion such that there

could be a selection of those troponin C sites

available for calcium ion binding that would

have associated cross-bridges in position to

take advantage of the emerging tight binding

site.

107.

R.W. Lymn and E.W. Taylor, "Mechanism of

ATP Hydrolysis by Actomyosin." Biochemistry,

10,

4617-4624,1971.

108.

T. Duke, "Cooperativity of Myosin Molecules

Through Strain-dependent Chemistry." Philos.

Trans. R. Soc.

Lond.

B, 355, 529-538, 2000.

109.

D.W. Urry, "Function of the Fi-motor (Fj-

ATPase) of ATP synthase by Apolar-polar

Repulsion through Internal Interfacial Water."

Cell Biology International, 30, (1), 44-55,2006.