the overall shape and activity of a protein, but a close interaction
between two, or more, different proteins may change completely
their conformation and physiological role. In this way, it was possible to understand the multiple role of some proteins, for instance
when they get in contact with other proteins inside a membrane,
giving rise to a receptor. This completely new approach renders very
actual the definition of allostery as “the second secret of life”,
prophetically disclosed by Jacques Monod [34] and subsequently
confirmed and extended by many others [35]. Thus, the supremacy
of proteins seems today to be definitely accepted.
References
1. Funke O (1851) €
Uber das Milzvenenblut.
Zeitschrift fu ¨r Ration Medizin 1:172–218
2. Mulder G (1838) Sur la composition de quelques substances animals. Bull des Sci Phys Nat
en Neerl 1:104
3. Ku ¨hne W (1877) €
Uber das Verhalten
verschiedener organisirter und sog. ungeformter
Fermente.
Verhandlungen
des
naturhistorisch-medicinischen Vereins zu Heidelberg. New Ser 1:190–193
4. Perutz MF, Rossmann MG, Cullis AF et al
(1960) Structure of haemoglobin. A threedimensional Fourier synthesis at 5.5-{A ˚ } resolution, obtained by X-ray analysis. Nature
185:416–422
5. Dahm R (2005) Friedrich Miescher and the
discovery of DNA. Dev Biol 278:274–288.
https://doi.org/10.1016/j.ydbio.2004.11.
028
6. Levene P (1919) The structure of yeast nucleic
acid. J Biol Chem 40:415–424
7. Watson JD, Crick FH, Pelz B et al (1953)
Molecular structure of nucleic acids; a structure
for deoxyribose nucleic acid. Nature
171:737–738. https://doi.org/10.1126/sci
ence.aaf5508
8. Lander ES, Linton LM, Birren B et al (2001)
Initial sequencing and analysis of the human
genome. Nature 409:860–921. https://doi.
org/10.1038/35057062
9. Ohno S (1972) So much ‘junk’ DNA in our
genome. Brookhaven Symp Biol 23:366–370
10. Pennisi E (2012) ENCODE project writes
eulogy
for
junk
DNA.
Science
337:1159–1161. https://doi.org/10.1126/
science.337.6099.1159
11. Fedor MJ, Williamson JR (2005) The catalytic
diversity of RNAs. Nat Rev Mol Cell Biol
6:399–412.
https://doi.org/10.1038/
nrm1647
12. Lee K-Y, Lee B (2017) Structural and biochemical properties of novel self-cleaving ribozymes. Molecules 22:678. https://doi.org/10.
3390/molecules22040678
13. Robertson MP, Joyce GF (2012) The origins of
the RNA World. Cold Spring Harb Perspect
Biol
4:1.
https://doi.org/10.1101/
cshperspect.a003608
14. Higgs PG, Lehman N (2014) The RNA World:
molecular cooperation at the origins of life. Nat
Rev Genet 16:7–17. https://doi.org/10.
1038/nrg3841
15. Changeux JP (2011) 50th anniversary of the
word ‘allosteric’. Protein Sci 20:1119–1124.
https://doi.org/10.1002/pro.658
16. Dokholyan NV (2016) Controlling allosteric
networks in proteins. Chem Rev 116
(11):6463–6487. https://doi.org/10.1021/
acs.chemrev.5b00544
17. Ca ´rdenas ML (2013) Michaelis and Menten
and the long road to the discovery of cooperativity. FEBS Lett 587:2767–2771. https://doi.
org/10.1016/j.febslet.2013.07.014
18. Cornish-Bowden A (2014) Understanding
allosteric and cooperative interactions in
enzymes. FEBS J 281:621–632. https://doi.
org/10.1111/febs.12469
19. Swain JF, Gierasch LM (2006) The changing
landscape of protein allostery. Curr Opin Struct
Biol 16:102–108. https://doi.org/10.1016/j.
sbi.2006.01.003
20. Motlagh HN, Wrabl JO, Li J, Hilser VJ (2014)
The ensemble nature of allostery. Nature
508:331–339.
https://doi.org/10.1038/
nature13001
21. Gunasekaran K, Ma B, Nussinov R (2004) Is
allostery an intrinsic property of all dynamic
proteins? Proteins 57:433–443
22. Nussinov R (2016) Introduction to protein
ensembles and allostery. Chem Rev
Allostery: The Rebound of Proteins
5
between two, or more, different proteins may change completely
their conformation and physiological role. In this way, it was possible to understand the multiple role of some proteins, for instance
when they get in contact with other proteins inside a membrane,
giving rise to a receptor. This completely new approach renders very
actual the definition of allostery as “the second secret of life”,
prophetically disclosed by Jacques Monod [34] and subsequently
confirmed and extended by many others [35]. Thus, the supremacy
of proteins seems today to be definitely accepted.
References
1. Funke O (1851) €
Uber das Milzvenenblut.
Zeitschrift fu ¨r Ration Medizin 1:172–218
2. Mulder G (1838) Sur la composition de quelques substances animals. Bull des Sci Phys Nat
en Neerl 1:104
3. Ku ¨hne W (1877) €
Uber das Verhalten
verschiedener organisirter und sog. ungeformter
Fermente.
Verhandlungen
des
naturhistorisch-medicinischen Vereins zu Heidelberg. New Ser 1:190–193
4. Perutz MF, Rossmann MG, Cullis AF et al
(1960) Structure of haemoglobin. A threedimensional Fourier synthesis at 5.5-{A ˚ } resolution, obtained by X-ray analysis. Nature
185:416–422
5. Dahm R (2005) Friedrich Miescher and the
discovery of DNA. Dev Biol 278:274–288.
https://doi.org/10.1016/j.ydbio.2004.11.
028
6. Levene P (1919) The structure of yeast nucleic
acid. J Biol Chem 40:415–424
7. Watson JD, Crick FH, Pelz B et al (1953)
Molecular structure of nucleic acids; a structure
for deoxyribose nucleic acid. Nature
171:737–738. https://doi.org/10.1126/sci
ence.aaf5508
8. Lander ES, Linton LM, Birren B et al (2001)
Initial sequencing and analysis of the human
genome. Nature 409:860–921. https://doi.
org/10.1038/35057062
9. Ohno S (1972) So much ‘junk’ DNA in our
genome. Brookhaven Symp Biol 23:366–370
10. Pennisi E (2012) ENCODE project writes
eulogy
for
junk
DNA.
Science
337:1159–1161. https://doi.org/10.1126/
science.337.6099.1159
11. Fedor MJ, Williamson JR (2005) The catalytic
diversity of RNAs. Nat Rev Mol Cell Biol
6:399–412.
https://doi.org/10.1038/
nrm1647
12. Lee K-Y, Lee B (2017) Structural and biochemical properties of novel self-cleaving ribozymes. Molecules 22:678. https://doi.org/10.
3390/molecules22040678
13. Robertson MP, Joyce GF (2012) The origins of
the RNA World. Cold Spring Harb Perspect
Biol
4:1.
https://doi.org/10.1101/
cshperspect.a003608
14. Higgs PG, Lehman N (2014) The RNA World:
molecular cooperation at the origins of life. Nat
Rev Genet 16:7–17. https://doi.org/10.
1038/nrg3841
15. Changeux JP (2011) 50th anniversary of the
word ‘allosteric’. Protein Sci 20:1119–1124.
https://doi.org/10.1002/pro.658
16. Dokholyan NV (2016) Controlling allosteric
networks in proteins. Chem Rev 116
(11):6463–6487. https://doi.org/10.1021/
acs.chemrev.5b00544
17. Ca ´rdenas ML (2013) Michaelis and Menten
and the long road to the discovery of cooperativity. FEBS Lett 587:2767–2771. https://doi.
org/10.1016/j.febslet.2013.07.014
18. Cornish-Bowden A (2014) Understanding
allosteric and cooperative interactions in
enzymes. FEBS J 281:621–632. https://doi.
org/10.1111/febs.12469
19. Swain JF, Gierasch LM (2006) The changing
landscape of protein allostery. Curr Opin Struct
Biol 16:102–108. https://doi.org/10.1016/j.
sbi.2006.01.003
20. Motlagh HN, Wrabl JO, Li J, Hilser VJ (2014)
The ensemble nature of allostery. Nature
508:331–339.
https://doi.org/10.1038/
nature13001
21. Gunasekaran K, Ma B, Nussinov R (2004) Is
allostery an intrinsic property of all dynamic
proteins? Proteins 57:433–443
22. Nussinov R (2016) Introduction to protein
ensembles and allostery. Chem Rev
Allostery: The Rebound of Proteins
5