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Control of Enzyme function through loop dynamics
Author(s) -
Chi Celestine N.,
Vogeli Beat,
Bibow Stefan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.835.2
Subject(s) - allosteric regulation , protein dynamics , function (biology) , dynamics (music) , active site , domain (mathematical analysis) , chemistry , biophysics , enzyme , protein structure , computational biology , physics , biochemistry , biology , microbiology and biotechnology , mathematics , mathematical analysis , acoustics
Allosteric regulation has been revealed as an essential property of all proteins. Dynamic shift of structural equilibrium at one site can have structural and functional effect at other sites. However for small, single domain proteins these phenomena is difficult to access, albeit quantify easily. One way of shifting structural equilibrium distribution is by changing the the dynamics of flexible loops by amino acid substitution because large changes maybe achieved with minimal modification of protein. A ligand‐selective change of the binding affinity to the active‐site of the enzyme cyclophlin by tuning the dynamics of a highly flexible loop is presented. This system may serve as a platform to study the effects of various timescales of loop motion on protein function turned by mutations and opens the possibility for elucidating the role of time‐scale dependent allostery Support or Funding Information This work was support in part by the Swedish research council Wenner‐Gren Stiftelsern WG‐13, Postdoctoral fellowship to C. N. Chi, the Swiss National Science Foundation with Grant 140214 and ETH Research Grant ETH‐04 13‐1 to B. Vögeli.