independent dynamic segments: an extended
view of binding events. Trends Biochem Sci
35(10):539–546
4. Nussinov R, Ma B, Tsai CJ (2014) Multiple
conformational selection and induced fit
events take place in allosteric propagation.
Biophys Chem 186:22–30
5. Michel D (2016) Conformational selection or
induced fit? New insights from old principles.
Biochimie 128-129:48–54
6. Changeux JP, Edelstein S (2011) Conformational selection or induced fit? 50 years of
debate resolved. F1000 Biol Rep 3(19):1–15
7. Frederick KK, Marlow MS, Valentine KG,
Wand AJ (2007) Conformational entropy in
molecular recognition by proteins. Nature
448(7151):325–329
8. Gianni S, Dogan J, Jemth P (2014) Distinguishing induced fit from conformational
selection. Biophys Chem 189:33–39
9. Hammes GG, Chang Y, Oas TG (2009) Conformational selection or induced fit: a flux
description of reaction mechanism. Proc Natl
Acad Sci U S A 106(33):13434–13741
10. Hatzakis NS (2014) Single molecule insights
on conformational selection and induced fit
mechanism. Biophys Chem 186:46–54
11. Ma B, Nussinov R (2010) Enzyme dynamics
point to stepwise conformational selection in
catalysis. Curr Opin Chem Biol 14
(5):652–659
12. Teague SJ (2003) Implications of protein flexibility for drug discovery. Nat Rev Drug Discov 2(7):527–541
13. Vega S, Abian O, Velazquez-Campoy A
(2016) On the link between conformational
changes, ligand binding and heat capacity.
Biochim Biophys Acta 1860(5):868–878
14. Vogt AD, Di Cera E (2013) Conformational
selection is a dominant mechanism of ligand
binding. Biochemistry 52(34):5723–5729
15. Watt ED, Shimada H, Kovrigin EL, Loria JP
(2007) The mechanism of rate-limiting
motions in enzyme function. Proc Natl Acad
Sci U S A 104(29):11981–11986
16. Weikl TR, Paul F (2014) Conformational
selection in protein binding and function.
Protein Sci 23(11):1508–1518
17. Zhou HX (2010) From induced fit to conformational selection: a continuum of binding
mechanism controlled by the timescale of
conformational transitions. Biophys J 98(6):
L15–L17
18. Schnell JR, Dyson HJ, Wright PE (2004)
Structure, dynamics, and catalytic function of
dihydrofolate reductase. Annu Rev Biophys
Biomol Struct 33:119–140
19. Eisenmesser EZ et al (2002) Enzyme dynamics
during
catalysis.
Science
295
(5559):1520–1523
20. Peng JW (2009) Communication breakdown:
protein dynamics and drug design. Structure
17(3):319–320
21. Sawaya MR, Kraut J (1997) Loop and subdomain movements in the mechanism of E. coli
DHFR-Crystallographic evidence. Biochemistry 36:586–603
22. Huennekens FM (1994) The methotraxate
story: a paradigm for development of cancer
chemotherapeutic agents. Adv Enzyme Regul
34:379–419
23. Fierke CA, Johnson KA, Benkovic SJ (1987)
Construction and evaluation of the Kinetic
Scheme associated with DHFR from Escherichia coli. Biochemistry 26:4085–4092
24. Verma CS, Caves LSD, Hubbard RE, Roberts
GCK (1997) Domain motions in dihydrofolate reductase: a molecular dynamics study. J
Mol Biol 266:776–796
25. Wallace LA, Robert Matthews C (2002)
Highly divergent dihydrofolate reductases
conserve complex folding mechanisms. J
Mol Biol 315(2):193–211
26. Matthews DA, Alden RA, Bolin JT, Freer ST,
Hamlin R, Xuong N, Kraut J, Poe M,
Williams M, Hoogsteen K (1977) DHFR-Xray structure of the binary complex with
methotrexate. Science 197(4302):452–455
27. Bystroff C, Kraut J (1991) Crystal structures
of E. coli DHFR-the NADP+ holoenzyme
and the folate-NADP+ complex. Substrate
binding and a model for the transition state.
Biochemistry 30:2227–2239
28. Petterson EF, Goddard TD, Huang CC,
Couch GS, Greenblatt DM, Meng EC, Ferrin
TE (2004) UCSF chimera--a visualization
system for exploratory research and analysis.
J Comput Chem 25(13):1605–1612
29. Bystroff C, Oatley SJ, Kraut J (1990) Crystal
structures of E. coli DHFR-the NADP+ holoenzyme and the folate-NADP+ complex. Substrate binding and a model for the transition
state. Biochemistry 29(13):3263–3277
30. Appleman JR, Howell EE, Kraut J, Blakely RL
(1990) Role of Aspartate 27 of DHFR from E
coli in interconversion of active and inactive
enzyme conformers and binding of NADPH.
J Biol Chem 265(10):5579–5584
31. Howell EE, Villafranca JE, Warren MS, Oatley SJ, Kraut J (1986) Functional role of
Aspartic acid-27 DHFR revealed by mutagenesis. Science 231(4742):1123–1128
Distal Regions Regulate Dihydrofolate Reductase-Ligand Interactions
215
view of binding events. Trends Biochem Sci
35(10):539–546
4. Nussinov R, Ma B, Tsai CJ (2014) Multiple
conformational selection and induced fit
events take place in allosteric propagation.
Biophys Chem 186:22–30
5. Michel D (2016) Conformational selection or
induced fit? New insights from old principles.
Biochimie 128-129:48–54
6. Changeux JP, Edelstein S (2011) Conformational selection or induced fit? 50 years of
debate resolved. F1000 Biol Rep 3(19):1–15
7. Frederick KK, Marlow MS, Valentine KG,
Wand AJ (2007) Conformational entropy in
molecular recognition by proteins. Nature
448(7151):325–329
8. Gianni S, Dogan J, Jemth P (2014) Distinguishing induced fit from conformational
selection. Biophys Chem 189:33–39
9. Hammes GG, Chang Y, Oas TG (2009) Conformational selection or induced fit: a flux
description of reaction mechanism. Proc Natl
Acad Sci U S A 106(33):13434–13741
10. Hatzakis NS (2014) Single molecule insights
on conformational selection and induced fit
mechanism. Biophys Chem 186:46–54
11. Ma B, Nussinov R (2010) Enzyme dynamics
point to stepwise conformational selection in
catalysis. Curr Opin Chem Biol 14
(5):652–659
12. Teague SJ (2003) Implications of protein flexibility for drug discovery. Nat Rev Drug Discov 2(7):527–541
13. Vega S, Abian O, Velazquez-Campoy A
(2016) On the link between conformational
changes, ligand binding and heat capacity.
Biochim Biophys Acta 1860(5):868–878
14. Vogt AD, Di Cera E (2013) Conformational
selection is a dominant mechanism of ligand
binding. Biochemistry 52(34):5723–5729
15. Watt ED, Shimada H, Kovrigin EL, Loria JP
(2007) The mechanism of rate-limiting
motions in enzyme function. Proc Natl Acad
Sci U S A 104(29):11981–11986
16. Weikl TR, Paul F (2014) Conformational
selection in protein binding and function.
Protein Sci 23(11):1508–1518
17. Zhou HX (2010) From induced fit to conformational selection: a continuum of binding
mechanism controlled by the timescale of
conformational transitions. Biophys J 98(6):
L15–L17
18. Schnell JR, Dyson HJ, Wright PE (2004)
Structure, dynamics, and catalytic function of
dihydrofolate reductase. Annu Rev Biophys
Biomol Struct 33:119–140
19. Eisenmesser EZ et al (2002) Enzyme dynamics
during
catalysis.
Science
295
(5559):1520–1523
20. Peng JW (2009) Communication breakdown:
protein dynamics and drug design. Structure
17(3):319–320
21. Sawaya MR, Kraut J (1997) Loop and subdomain movements in the mechanism of E. coli
DHFR-Crystallographic evidence. Biochemistry 36:586–603
22. Huennekens FM (1994) The methotraxate
story: a paradigm for development of cancer
chemotherapeutic agents. Adv Enzyme Regul
34:379–419
23. Fierke CA, Johnson KA, Benkovic SJ (1987)
Construction and evaluation of the Kinetic
Scheme associated with DHFR from Escherichia coli. Biochemistry 26:4085–4092
24. Verma CS, Caves LSD, Hubbard RE, Roberts
GCK (1997) Domain motions in dihydrofolate reductase: a molecular dynamics study. J
Mol Biol 266:776–796
25. Wallace LA, Robert Matthews C (2002)
Highly divergent dihydrofolate reductases
conserve complex folding mechanisms. J
Mol Biol 315(2):193–211
26. Matthews DA, Alden RA, Bolin JT, Freer ST,
Hamlin R, Xuong N, Kraut J, Poe M,
Williams M, Hoogsteen K (1977) DHFR-Xray structure of the binary complex with
methotrexate. Science 197(4302):452–455
27. Bystroff C, Kraut J (1991) Crystal structures
of E. coli DHFR-the NADP+ holoenzyme
and the folate-NADP+ complex. Substrate
binding and a model for the transition state.
Biochemistry 30:2227–2239
28. Petterson EF, Goddard TD, Huang CC,
Couch GS, Greenblatt DM, Meng EC, Ferrin
TE (2004) UCSF chimera--a visualization
system for exploratory research and analysis.
J Comput Chem 25(13):1605–1612
29. Bystroff C, Oatley SJ, Kraut J (1990) Crystal
structures of E. coli DHFR-the NADP+ holoenzyme and the folate-NADP+ complex. Substrate binding and a model for the transition
state. Biochemistry 29(13):3263–3277
30. Appleman JR, Howell EE, Kraut J, Blakely RL
(1990) Role of Aspartate 27 of DHFR from E
coli in interconversion of active and inactive
enzyme conformers and binding of NADPH.
J Biol Chem 265(10):5579–5584
31. Howell EE, Villafranca JE, Warren MS, Oatley SJ, Kraut J (1986) Functional role of
Aspartic acid-27 DHFR revealed by mutagenesis. Science 231(4742):1123–1128
Distal Regions Regulate Dihydrofolate Reductase-Ligand Interactions
215