INTRODUCTION

Enzyme catalysis and allostery: a century of advances inmolecular understandingAthel Cornish-Bowden

Centre National de la Recherche Scientifique and Aix-Marseille Universite, France

Numerous anniversaries of interest to biochemists have

occurred in 2013, starting from Claude Bernards birth

in 1813, continuing with Victor Henris thesis in 1903,

Johannes Brnsteds protonic theory of acidbasecatalysis in 1923, the introduction of flow methods for

investigating fast reaction kinetics by Hamilton Har-

tridge and Francis Roughton in the same year, Jim

Watson and Francis Cricks determination of the

structure of DNA in 1953, Mo Clelands rationaliza-

tion of multi-substrate kinetics in 1963, and Henrik

Kacser and Jim Burnss introduction of metabolic con-

trol analysis in 1973. Two others stand out for enzy-

mologists: in 1913, Leonor Michaelis and Maud

Leonora Menten placed kinetic studies on a firm

experimental and theoretical basis [1] and, in 1963,

Jacques Monod, Jean-Pierre Changeux and FrancoisJacob introduced the concept of allosteric regulation

[2]. In this special issue of the FEBS Journal (the suc-

cessor to the Biochemische Zeitschrift, where Michaelis

and Menten published their paper), we commemorate

the 100th anniversary of the former, and the 50th

anniversary of the latter. The continuing importance

of both is well illlustrated by the two recent transla-

tions of Michaelis and Mentens paper into English

[3,4], and by the many recent reviews of allosteric reg-

ulation and models of cooperativity.

In this special issue, Ute Deichmann and colleagues

examine the historical context of Michaelis and Men-

tens paper, and discuss its relationship to what was

already known at the time, from Henris work in par-

ticular. Moving to the present day, various authors

review the status of kinetics in modern research: Santi-

ago Schnell on the validity of the steady-state assump-

tion; Jeremy Gunawardena on time separation; Judith

Klinman on kinetic isotope effects; Jeffrey Moffitt and

Carlos Bustamante on single-molecule studies, a topic

also developed by Santiago Schnell and colleagues;

Hanna Hardin and colleagues on kinetic aspects of

protein networks, with particular reference to phos-

photransferases; and Katia Tummler and colleagues

on dynamic modelling of enzyme networks. Such mod-

elling requires the characterization not just of one

enzyme but of the whole network, and Ulrike Wittig

and colleagues describe the challenges involved in set-

ting up an enzyme reaction database. That in turn

depends heavily on the classification of enzyme reac-

tions, a topic that has been greatly developed under

the aegis of the International Union of Biochemistry

and Molecular Biology since 1958; Andrew MacDon-

ald and Keith Tipton review the achievements in this

field and the difficulties that can arise. Anyone who

reads Michaelis and Mentens classic paper today can

only be impressed by how much they knew, how much

they understood, and how much care they took with

their analysis. In the century since then, some points

have tended to become forgotten, and Roger Goody

discusses the problems that arise when kinetic analysis

is not conducted with sufficient care and attention.

The link between Michaelis and Menten in 1913 and

Monod, Changeux and Jacob in 1963 is made by

Debashish Chowdhury in the context of molecular

motors, and John Gerhart describes the historical con-

text in which the ideas of enzyme regulation arose. It is

perhaps surprising that 50 years separate the two

papers: why did it take so long for deviations

from MichaelisMenten kinetics to be reported and

Athel Cornish-Bowden learned about MichaelisMenten kinetics when he was working for his DPhil at Oxford with Jer-

emy Knowles, and his postdoctoral research in Dan Koshlands laboratory at Berkeley led to an interest in mechanisms

of enzyme regulation. Subsequently, he spent 16 years in the Biochemistry Department at Birmingham, before moving

to the CNRS in Marseilles in 1987, where he is now Directeur de Recherche Emerite. His principal research interests

in recent years have been self-organization and the definition of life. He is the longest-serving member of the Editorial-

Advisory Board of the FEBS Journal, which he joined in 1984.

doi: 10.1111/febs.12695

FEBS Journal 281 (2014) 433434 2013 FEBS 433

analysed? The explanation probably lies in the need to

establish the norm before exceptions to it could be rec-

ognized [5]: a century ago, extremely few enzymes had

been characterized, even superficially, and almost noth-

ing was known about their structures (this was in the

heyday of colloids) or about metabolic pathways and

how they might be regulated. The first paper on alloste-

ric interactions [2] continues to be well cited, although

perhaps overshadowed by the publication of models to

account for them [6,7] that it stimulated. The relation-

ship between these and other models is reviewed by

Athel Cornish-Bowden. Right from the outset haemo-

globin, as an honorary enzyme, was at the centre of

many discussions of these models because it offered

numerous advantages over any enzymes that had been

characterized 50 years ago, and it has continued to be

one of the most interesting and important examples of

allosteric regulation, as described by Maurizio Brunori.

Biochemistry has moved a long way from invertase

kinetics, first to allosteric regulation and the whole

development of metabolic regulation and control, and

now to detailed three-dimensional structures of

enzymes, details of their mechanisms of action, and,

most recently, studies of single molecules. In this spe-

cial issue of the FEBS Journal, we have attempted to

provide a rounded picture of this development.

References

1 Michaelis L & Menten ML (1913) Kinetik der

Invertinwirkung. Biochem Z 49, 333369.

2 Monod J, Changeux JP & Jacob F (1963) Allosteric

proteins and cellular control systems. J Mol Biol 6,

306329.

3 Johnson KA & Goody RS (2011) The original Michaelis

constant: translation of the 1913 MichaelisMenten

paper. Biochemistry 50, 82648269.

4 Michaelis L & Menten ML (2013) The kinetics of

invertin action (translated by T R C Boyde). FEBS Lett

587, 27122720.

5 Cardenas ML (2013) Michaelis and Menten and the long

road to the discovery of cooperativity. FEBS Lett 587,

27672771.

6 Monod J, Wyman J & Changeux JP (1965) On the

nature of allosteric transitions a plausible model.

J Mol Biol 12, 88118.

7 Koshland DE Jr, Nemethy G & Filmer D (1966)

Comparison of experimental binding data and

theoretical models in proteins containing subunits.

Biochemistry 5, 365385.

434 FEBS Journal 281 (2014) 433434 2013 FEBS

MichaelisMenten kinetics and allosteric regulation A. Cornish-Bowden