title: 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.
authors: Joint BSC-CRG-IRB Research Programme in Computational Biology, Barcelona Supercomputing Center - BSC, Barcelona, Spain.
authors: Santiago
authors: S
authors: Esteban-Martín
authors: Joint BSC-CRG-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine - IRB Barcelona, Barcelona, Spain.
authors: Robert Bryn
authors: RB
authors: Fenwick
authors: Department of Chemistry, Chemical Biological Centre, Umeå University, Umeå, Sweden.
authors: Jörgen
authors: J
authors: Ådén
authors: Joint BSC-CRG-IRB Research Programme in Computational Biology, Barcelona Supercomputing Center - BSC, Barcelona, Spain.
authors: Benjamin
authors: B
authors: Cossins
authors: Joint BSC-CRG-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine - IRB Barcelona, Barcelona, Spain.
authors: Carlos W
authors: CW
authors: Bertoncini
authors: Joint BSC-CRG-IRB Research Programme in Computational Biology, Barcelona Supercomputing Center - BSC, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats - ICREA, Barcelona, Spain.
authors: Victor
authors: V
authors: Guallar
authors: Department of Chemistry, Chemical Biological Centre, Umeå University, Umeå, Sweden.
authors: Magnus
authors: M
authors: Wolf-Watz
authors: Joint BSC-CRG-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine - IRB Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats - ICREA, Barcelona, Spain.
authors: Xavier
authors: X
authors: Salvatella
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry* / Q000378:metabolism*; D000465:Algorithms; D000494:Allosteric Regulation; D019295:Computational Biology; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary
chemical_list: D000263:Adenylate Kinase