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Binding Leverage as a Molecular Basis for Allosteric Regulation 英文参考文献
BindingLeverageasaMolecularBasisforAllosteric
Regulation
SimonMitternacht1,2,IgorN.Berezovsky1*
1ComputationalBiologyUnit/UNIResearch,UniversityofBergen,Bergen,Norway,2DepartmentofInformatics,UniversityofBergen,Bergen,Norway
Abstract
Allostericregulationinvolvesconformationaltransitionsorfluctuationsbetweenafewcloselyrelatedstates,causedbythe
bindingofeffectormolecules.Weintroduceaquantitycalledbindingleveragethatmeasurestheabilityofabindingsiteto
coupletotheintrinsicmotionsofaprotein.WeuseMonteCarlosimulationstogeneratepotentialbindingsitesandeither
normal modes or pairs of crystal structures to describe relevant motions. We analyze single catalytic domains and
multimericallostericenzymeswithcomplexregulation.Forthemajorityoftheanalyzedproteins,wefindthatbothcatalytic
and allosteric sites have high binding leverage. Furthermore, our analysis of the catabolite activator protein, which is
allostericwithoutconformationalchange,showsthatitsregulationinvolvesothertypesofmotionthanthosemodulatedat
siteswithhighbindingleverage.Ourresultspointtotheimportanceofincorporatingdynamicinformationwhenpredicting
functional sites. Because it is possible to calculate binding leverage from a single crystal structure it can be used for
characterizingproteinsofunknownfunctionandpredictinglatentallostericsitesinanyprotein,withimplicationsfordrug
design.
Citation: Mitternacht S,BerezovskyIN (2011) Binding Leverage asa Molecular Basis for Allosteric Regulation. PLoS Comput Biol 7(9): e1002148. doi:10.1371/
journal.pcbi.1002148
Editor:ThomasLengauer,Max-Planck-Institutfu¨rInformatik,Germany
ReceivedApril5,2011;AcceptedJune21,2011;PublishedSeptember15,2011
Copyright: ? 2011 Mitternacht, Berezovsky. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ThisstudywasfundedbytheNorwegianResearchCouncil.Thefundershadnorole
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