Enzyme dynamics point to stepwise conformational selection in catalysis.
Recent data increasingly reveal that conformational dynamics are indispensable to enzyme function throughout the catalytic cycle, in substrate recruiting, chemical transformation, and product release. Conformational transitions may involve conformational selection and induced fit, which can be viewed as a special case in the catalytic network. NMR, X-ray crystallography, single-molecule FRET, and simulations clearly demonstrate that the free enzyme dynamics already encompass all the conformations necessary for substrate binding, preorganization, transition-state stabilization, and product release. Conformational selection and substate population shift at each step of the catalytic turnover can accommodate enzyme specificity and efficiency. Within such a framework, entropy can have a larger role in conformational dynamics than in direct energy transfer in dynamically promoted catalysis.
Ma
Buyong
B
Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA. mabuyong@mail.nih.gov
Nussinov
Ruth
R
D055162:Biocatalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D013379:Substrate Specificity
D004798:Enzymes
RNA. 2009 Aug;15(8):1565-77
19549719
Protein Sci. 2000 Jan;9(1):10-9
10739242
Biochemistry. 2008 Mar 18;47(11):3317-21
18298083
Biochemistry. 2009 Jun 16;48(23):5226-38
19425594
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1373-8
20080605
Proteins. 2010 May 1;78(6):1339-75
20099310
Biochemistry. 2009 Jun 16;48(23):5057-65
19435325
Nat Chem Biol. 2009 Nov;5(11):789-96
19841628
Acc Chem Res. 2005 Dec;38(12):923-31
16359164
Phys Rev E Stat Nonlin Soft Matter Phys. 2006 Jan;73(1 Pt 1):010902
16486113
J Am Chem Soc. 2008 Jun 11;130(23):7477-88
18479090
J Biol Chem. 2009 Jan 2;284(1):207-217
18955494
J Phys Chem A. 2009 Nov 12;113(45):12439-46
19534504
J Theor Biol. 2000 Apr 21;203(4):383-97
10736215
Nat Chem Biol. 2009 Oct;5(10):758-64
19718043
Science. 2006 Sep 15;313(5793):1638-42
16973882
Nature. 2007 Dec 13;450(7172):964-72
18075575
Nature. 2009 Oct 29;461(7268):1300-4
19865174
Science. 2009 Apr 17;324(5925):407-10
19372434
Biophys J. 2006 May 15;90(10):3365-74
16500972
ACS Chem Biol. 2010 Mar 19;5(3):265-72
20151694
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17359-64
19805169
Biochemistry. 2009 Oct 13;48(40):9599-605
19728743
PLoS Biol. 2009 Oct;7(10):e1000225
19859523
Protein Sci. 2002 Feb;11(2):184-97
11790828
J Am Chem Soc. 2009 Dec 2;131(47):17072-3
19891489
Structure. 2009 Oct 14;17(10):1356-67
19836335
J Am Chem Soc. 2008 Nov 19;130(46):15361-73
18939839
J Phys Chem B. 2006 Oct 19;110(41):20093-7
17034179
Nature. 2009 Dec 3;462(7273):669-73
19956261
J Biol Chem. 2008 Feb 1;283(5):2846-57
18039651
FEBS Lett. 2010 Jan 4;584(1):203-6
19932101
Protein Eng. 1999 Sep;12(9):713-20
10506280
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2775-80
20133612
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2794-9
11867722
J Biol Chem. 2007 Sep 28;282(39):28884-28892
17640877
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):715-20
20080740
Nature. 2005 Nov 3;438(7064):117-21
16267559
J Biol Chem. 2010 Mar 26;285(13):9594-9603
20097757
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21631-6
19966226
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13829-34
18772387
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6807-12
15811945
Proteins. 2009 Apr;75(1):104-10
18798570
Biochemistry. 2008 Oct 14;47(41):10991-8
18798649
Biochemistry. 2009 Aug 4;48(30):7160-8
19588901
Protein Sci. 2009 May;18(5):1003-11
19388022
Structure. 2009 Aug 12;17(8):1137-47
19679091
J Chem Phys. 2009 Aug 14;131(6):065104
19691414
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2740-5
20133613
PLoS Comput Biol. 2007 Jun;3(6):e117
17571919
Biochemistry. 2009 Dec 8;48(48):11335-43
19835417
Biochemistry. 2010 Mar 9;49(9):2058-67
20108972
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16543-8
18946041
J Am Chem Soc. 2008 Apr 9;130(14):4772-83
18338887
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16203-8
19805281
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13737-41
19666553
Nature. 2007 Oct 25;449(7165):1078-82
17960247
Nat Struct Mol Biol. 2010 Jan;17(1):99-104
19966797
Nature. 2007 Dec 6;450(7171):838-44
18026086
Nat Chem Biol. 2009 Aug;5(8):551-8
19620996
J Biol Chem. 2009 Jul 31;284(31):21090-9
19515847