Detailed Structure of the H2PO4鈥?/sup>鈥揋uanosine Diphosphate Intermediate in Ras-GAP Decoded from FTIR Experiments by Biomolecular Simulations
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- 作者：Fei Xia ; Till Rudack ; Qiang Cui ; Carsten K枚tting ; Klaus Gerwert
- 刊名：The Journal of the American Chemical Society
- 出版年：2012
- 出版时间：December 12, 2012
- 年：2012
- 卷：134
- 期：49
- 页码：20041-20044
- 全文大小：249K
- 年卷期：v.134,no.49(December 12, 2012)
- ISSN：1520-5126
文摘
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)鈥揌2PO4鈥?/sup> intermediate, in the surrounding protein鈥損rotein 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 H2PO4鈥?/sup> 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.