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Correlated inter-domain motions in adenylate kinase.

ABSTRACT: Correlated inter-domain motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. Here we characterize at structural level the inter-domain coupling in a multidomain enzyme, Adenylate Kinase (AK), using computational methods that exploit the shape information encoded in residual dipolar couplings (RDCs) measured under steric alignment by nuclear magnetic resonance (NMR). We find experimental evidence for a multi-state equilibrium distribution along the opening/closing pathway of Adenylate Kinase, previously proposed from computational work, in which inter-domain interactions disfavour states where only the AMP binding domain is closed. In summary, we provide a robust experimental technique for study of allosteric regulation in AK and other enzymes.

SUBMITTER: Esteban-Martin S

PROVIDER: S-EPMC4117416 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Correlated inter-domain motions in adenylate kinase.

Esteban-Martín Santiago S Fenwick Robert Bryn RB Ådén Jörgen J Cossins Benjamin B Bertoncini Carlos W CW Guallar Victor V Wolf-Watz Magnus M Salvatella Xavier X

PLoS computational biology 20140731 7

Correlated inter-domain motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. Here we characterize at structural level the inter-domain coupling in a multidomain enzyme, Adenylate Kinase (AK), using computational methods that exploit the shape information encoded in residual dipolar couplings (RDCs) measured under steric alignment by nuclear magnetic resonance (NMR). We find experimental evidence for a multi-state equilibrium distribution al ...[more]

PMID: 25078441

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