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Protein Allostery at Atomic Resolution
Author(s) -
Strotz Dean,
Orts Julien,
Kadavath Harindranath,
Friedmann Michael,
Ghosh Dhiman,
Olsson Simon,
Chi Celestine N.,
Pokharna Aditya,
Güntert Peter,
Vögeli Beat,
Riek Roland
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008734
Subject(s) - allosteric regulation , chemistry , allosteric enzyme , ligand (biochemistry) , biophysics , microsecond , protein dynamics , population , domain (mathematical analysis) , protein domain , protein structure , chemical physics , physics , enzyme , biochemistry , biology , receptor , demography , astronomy , sociology , gene , mathematical analysis , mathematics
Abstract Protein allostery is a phenomenon involving the long range coupling between two distal sites in a protein. In order to elucidate allostery at atomic resoluion on the ligand‐binding WW domain of the enzyme Pin1, multistate structures were calculated from exact nuclear Overhauser effect (eNOE). In its free form, the protein undergoes a microsecond exchange between two states, one of which is predisposed to interact with its parent catalytic domain. In presence of the positive allosteric ligand, the equilibrium between the two states is shifted towards domain–domain interaction, suggesting a population shift model. In contrast, the allostery‐suppressing ligand decouples the side‐chain arrangement at the inter‐domain interface thereby reducing the inter‐domain interaction. As such, this mechanism is an example of dynamic allostery. The presented distinct modes of action highlight the power of the interplay between dynamics and function in the biological activity of proteins.