title: Enzyme dynamics point to stepwise conformational selection in catalysis.
abstract: 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.
authors.affiliation: Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA. mabuyong@mail.nih.gov
authors.forename: Buyong
authors.initials: B
authors.lastname: Ma
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D055162:Biocatalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D004798:Enzymes
references.citation: RNA. 2009 Aug;15(8):1565-77
references.pmid: 19549719
references.citation: Protein Sci. 2000 Jan;9(1):10-9
references.pmid: 10739242
references.citation: Biochemistry. 2008 Mar 18;47(11):3317-21
references.pmid: 18298083
references.citation: Biochemistry. 2009 Jun 16;48(23):5226-38
references.pmid: 19425594
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1373-8
references.pmid: 20080605
references.citation: Proteins. 2010 May 1;78(6):1339-75
references.pmid: 20099310
references.citation: Biochemistry. 2009 Jun 16;48(23):5057-65
references.pmid: 19435325
references.citation: Nat Chem Biol. 2009 Nov;5(11):789-96
references.pmid: 19841628
references.citation: Acc Chem Res. 2005 Dec;38(12):923-31
references.pmid: 16359164
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2006 Jan;73(1 Pt 1):010902
references.pmid: 16486113
references.citation: J Am Chem Soc. 2008 Jun 11;130(23):7477-88
references.pmid: 18479090
references.citation: J Biol Chem. 2009 Jan 2;284(1):207-217
references.pmid: 18955494
references.citation: J Phys Chem A. 2009 Nov 12;113(45):12439-46
references.pmid: 19534504
references.citation: J Theor Biol. 2000 Apr 21;203(4):383-97
references.pmid: 10736215
references.citation: Nat Chem Biol. 2009 Oct;5(10):758-64
references.pmid: 19718043
references.citation: Science. 2006 Sep 15;313(5793):1638-42
references.pmid: 16973882
references.citation: Nature. 2007 Dec 13;450(7172):964-72
references.pmid: 18075575
references.citation: Nature. 2009 Oct 29;461(7268):1300-4
references.pmid: 19865174
references.citation: Science. 2009 Apr 17;324(5925):407-10
references.pmid: 19372434
references.citation: Biophys J. 2006 May 15;90(10):3365-74
references.pmid: 16500972
references.citation: ACS Chem Biol. 2010 Mar 19;5(3):265-72
references.pmid: 20151694
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17359-64
references.pmid: 19805169
references.citation: Biochemistry. 2009 Oct 13;48(40):9599-605
references.pmid: 19728743
references.citation: PLoS Biol. 2009 Oct;7(10):e1000225
references.pmid: 19859523
references.citation: Protein Sci. 2002 Feb;11(2):184-97
references.pmid: 11790828
references.citation: J Am Chem Soc. 2009 Dec 2;131(47):17072-3
references.pmid: 19891489
references.citation: Structure. 2009 Oct 14;17(10):1356-67
references.pmid: 19836335
references.citation: J Am Chem Soc. 2008 Nov 19;130(46):15361-73
references.pmid: 18939839
references.citation: J Phys Chem B. 2006 Oct 19;110(41):20093-7
references.pmid: 17034179
references.citation: Nature. 2009 Dec 3;462(7273):669-73
references.pmid: 19956261
references.citation: J Biol Chem. 2008 Feb 1;283(5):2846-57
references.pmid: 18039651
references.citation: FEBS Lett. 2010 Jan 4;584(1):203-6
references.pmid: 19932101
references.citation: Protein Eng. 1999 Sep;12(9):713-20
references.pmid: 10506280
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2775-80
references.pmid: 20133612
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2794-9
references.pmid: 11867722
references.citation: J Biol Chem. 2007 Sep 28;282(39):28884-28892
references.pmid: 17640877
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):715-20
references.pmid: 20080740
references.citation: Nature. 2005 Nov 3;438(7064):117-21
references.pmid: 16267559
references.citation: J Biol Chem. 2010 Mar 26;285(13):9594-9603
references.pmid: 20097757
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21631-6
references.pmid: 19966226
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13829-34
references.pmid: 18772387
references.citation: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6807-12
references.pmid: 15811945
references.citation: Proteins. 2009 Apr;75(1):104-10
references.pmid: 18798570
references.citation: Biochemistry. 2008 Oct 14;47(41):10991-8
references.pmid: 18798649
references.citation: Biochemistry. 2009 Aug 4;48(30):7160-8
references.pmid: 19588901
references.citation: Protein Sci. 2009 May;18(5):1003-11
references.pmid: 19388022
references.citation: Structure. 2009 Aug 12;17(8):1137-47
references.pmid: 19679091
references.citation: J Chem Phys. 2009 Aug 14;131(6):065104
references.pmid: 19691414
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2740-5
references.pmid: 20133613
references.citation: PLoS Comput Biol. 2007 Jun;3(6):e117
references.pmid: 17571919
references.citation: Biochemistry. 2009 Dec 8;48(48):11335-43
references.pmid: 19835417
references.citation: Biochemistry. 2010 Mar 9;49(9):2058-67
references.pmid: 20108972
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16543-8
references.pmid: 18946041
references.citation: J Am Chem Soc. 2008 Apr 9;130(14):4772-83
references.pmid: 18338887
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16203-8
references.pmid: 19805281
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13737-41
references.pmid: 19666553
references.citation: Nature. 2007 Oct 25;449(7165):1078-82
references.pmid: 17960247
references.citation: Nat Struct Mol Biol. 2010 Jan;17(1):99-104
references.pmid: 19966797
references.citation: Nature. 2007 Dec 6;450(7171):838-44
references.pmid: 18026086
references.citation: Nat Chem Biol. 2009 Aug;5(8):551-8
references.pmid: 19620996
references.citation: J Biol Chem. 2009 Jul 31;284(31):21090-9
references.pmid: 19515847