TY - JOUR
T1 - Crystallographic evidence for substrate-assisted GTP hydrolysis by a small GTP binding protein
AU - Pasqualato, Sebastiano
AU - Cherfils, Jacqueline
PY - 2005/4
Y1 - 2005/4
N2 - GTP hydrolysis by small GTP binding proteins of the Ras superfamily is a universal reaction that controls multiple cellular regulations. Its enzymic mechanism has been the subject of long-standing debates as to the existence/identity of the general base and the electronic nature of its transition state. Here we report the high-resolution crystal structure of a small GTP binding protein, Rab11, solved in complex with GDP and Pi. Unexpectedly, a Pi oxygen and the GDP-cleaved oxygen are located less than 2.5 Å apart, suggesting that they share a proton, likely in the form of a low-barrier hydrogen bond. This implies that the γ-phosphate of GTP was protonated; hence, that GTP acts as a general base. Furthermore, this interaction should establish at, and stabilize, the transition state. Altogether, we propose a revised model for the GTPase reaction that should reconcile earlier models into a unique substrate-assisted mechanism.
AB - GTP hydrolysis by small GTP binding proteins of the Ras superfamily is a universal reaction that controls multiple cellular regulations. Its enzymic mechanism has been the subject of long-standing debates as to the existence/identity of the general base and the electronic nature of its transition state. Here we report the high-resolution crystal structure of a small GTP binding protein, Rab11, solved in complex with GDP and Pi. Unexpectedly, a Pi oxygen and the GDP-cleaved oxygen are located less than 2.5 Å apart, suggesting that they share a proton, likely in the form of a low-barrier hydrogen bond. This implies that the γ-phosphate of GTP was protonated; hence, that GTP acts as a general base. Furthermore, this interaction should establish at, and stabilize, the transition state. Altogether, we propose a revised model for the GTPase reaction that should reconcile earlier models into a unique substrate-assisted mechanism.
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U2 - 10.1016/j.str.2005.01.014
DO - 10.1016/j.str.2005.01.014
M3 - Article
C2 - 15837192
AN - SCOPUS:17044438607
VL - 13
SP - 533
EP - 540
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 4
ER -