title: Detailed structure of the H2PO4(-)-guanosine diphosphate intermediate in Ras-GAP decoded from FTIR experiments by biomolecular simulations.
abstract: Essential biochemical processes such as signal transduction, energy conversion, or substrate conversion depend on transient ligand binding. Thus, identifying the detailed structure and transient positioning of small ligands, and their stabilization by the surrounding protein, is of great importance. In this study, by decoding information from Fourier transform infrared (FTIR) spectra with biomolecular simulation methods, we identify the precise position and hydrogen network of a small compound, the guanosine diphosphate (GDP)-H(2)PO(4)(-) intermediate, in the surrounding protein-protein complex of Ras and its GTPase-activating protein, a central molecular switch in cellular signal transduction. We validate the simulated structure by comparing the calculated fingerprint vibrational modes of H(2)PO(4)(-) with those obtained from FTIR experiments. The new structural information, below the resolution of X-ray structural analysis, gives detailed insight into the catalytic mechanism.
authors.affiliation: Chinese Academy of Sciences-Max Planck Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xia
authors.forename: Till
authors.initials: T
authors.lastname: Rudack
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cui
authors.forename: Carsten
authors.initials: C
authors.lastname: Kötting
authors.forename: Klaus
authors.initials: K
authors.lastname: Gerwert
mesh_terms: D006153:Guanosine Diphosphate / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D020703:ras GTPase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010710:Phosphates; D020703:ras GTPase-Activating Proteins; D006153:Guanosine Diphosphate