Escherichia coli adenylate kinase dynamics: comparison of elastic network model modes with mode-coupling (15)N-NMR relaxation data.
The dynamics of adenylate kinase of Escherichia coli (AKeco) and its complex with the inhibitor AP(5)A, are characterized by correlating the theoretical results obtained with the Gaussian Network Model (GNM) and the anisotropic network model (ANM) with the order parameters and correlation times obtained with Slowly Relaxing Local Structure (SRLS) analysis of (15)N-NMR relaxation data. The AMPbd and LID domains of AKeco execute in solution large amplitude motions associated with the catalytic reaction Mg(+2)*ATP + AMP --> Mg(+2)*ADP + ADP. Two sets of correlation times and order parameters were determined by NMR/SRLS for AKeco, attributed to slow (nanoseconds) motions with correlation time tau( perpendicular) and low order parameters, and fast (picoseconds) motions with correlation time tau( parallel) and high order parameters. The structural connotation of these patterns is examined herein by subjecting AKeco and AKeco*AP(5)A to GNM analysis, which yields the dynamic spectrum in terms of slow and fast modes. The low/high NMR order parameters correlate with the slow/fast modes of the backbone elucidated with GNM. Likewise, tau( parallel) and tau( perpendicular) are associated with fast and slow GNM modes, respectively. Catalysis-related domain motion of AMPbd and LID in AKeco, occurring per NMR with correlation time tau( perpendicular), is associated with the first and second collective slow (global) GNM modes. The ANM-predicted deformations of the unliganded enzyme conform to the functional reconfiguration induced by ligand-binding, indicating the structural disposition (or potential) of the enzyme to bind its substrates. It is shown that NMR/SRLS and GNM/ANM analyses can be advantageously synthesized to provide insights into the molecular mechanisms that control biological function.
Temiz
N Alpay
NA
Center for Computational Biology & Bioinformatics, Department of Biochemistry and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Meirovitch
Eva
E
Bahar
Ivet
I
D000263:Adenylate Kinase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D018360:Crystallography, X-Ray; D004548:Elasticity; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009068:Movement; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results
D008024:Ligands; D009587:Nitrogen Isotopes; D000263:Adenylate Kinase