PDBsum entry 6r3v

Hydrolase

PDB id: 6r3v

Contents

Protein chains

198 a.a.

172 a.a.

Ligands

PO4 ×2

MES

GDP

DTT

Metals

_MG

Waters ×254

References listed in PDB file

Key reference

• Title: A gap-Gtpase-Gdp-P_I intermediate crystal structure analyzed by dft shows gtp hydrolysis involves serial proton transfers.
• Authors: R.W.Molt, E.Pellegrini, Y.Jin.
• Ref.: Chemistry, 2019, 25, 8484-8488. [DOI no: 10.1002/chem.201901627]
• PubMed id: 31038818

Abstract

Cell 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 (P_i ). 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-P_i . Its 1.75 Å crystal structure shows geometry for ionic and hydrogen bond coordination of GDP and P_i 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 P_i release.