6r3v
Crystal Structure of RhoA-GDP-Pi in Complex with RhoGAPCrystal Structure of RhoA-GDP-Pi in Complex with RhoGAP
Structural highlights
FunctionRHG01_HUMAN GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate. Publication Abstract from PubMedCell signaling by small G proteins uses an ON to OFF signal based on conformational changes following the hydrolysis of GTP to GDP and release of dihydrogen phosphate (Pi). The catalytic mechanism of GTP hydrolysis by RhoA is strongly accelerated by a GAP protein and is now well defined, but timing of inorganic phosphate release and signal change remains unresolved. We have generated a quaternary complex for RhoA-GAP-GDP-Pi. Its 1.75 A crystal structure shows geometry for ionic and hydrogen bond coordination of GDP and Pi in an intermediate state. It enables the selection of a QM core for DFT exploration of a 20 H-bonded network. This identifies serial locations of the two mobile protons from the original nucleophilic water molecule, showing how they move in three rational steps to form a stable quaternary complex. It also suggests how two additional proton transfer steps can facilitate Pi release. A GAP-GTPase-GDP-Pi Intermediate Crystal Structure Analyzed by DFT Shows GTP Hydrolysis Involves Serial Proton Transfers.,Jin Y, Molt RW Jr, Pellegrini E Chemistry. 2019 Apr 30. doi: 10.1002/chem.201901627. PMID:31038818[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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