 |
PDBsum entry 4hlq
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase activator/protein transport
|
PDB id
|
|
|
|
4hlq
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Catalytic mechanism of a mammalian rab·rabgap complex in atomic detail.
|
|
|
Authors
|
|
K.Gavriljuk,
E.M.Gazdag,
A.Itzen,
C.Kötting,
R.S.Goody,
K.Gerwert.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2012,
109,
21348-21353.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Rab GTPases, key regulators of vesicular transport, hydrolyze GTP very slowly
unless assisted by Rab GTPase-activating proteins (RabGAPs). Dysfunction of
RabGAPs is involved in many diseases. By combining X-ray structure analysis and
time-resolved FTIR spectroscopy we reveal here the detailed molecular reaction
mechanism of a complex between human Rab and RabGAP at the highest possible
spatiotemporal resolution and in atomic detail. A glutamine residue of Rab
proteins (cis-glutamine) that is essential for intrinsic activity is less
important in the GAP-activated reaction. During generation of the
RabGAP·Rab:GTP complex, there is a rapid conformational change in which the
cis-glutamine is replaced by a glutamine from RabGAP (trans-glutamine); this
differs from the RasGAP mechanism, where the cis-glutamine is also important for
GAP catalysis. However, as in the case of Ras, a trans-arginine is also
recruited to complete the active center during this conformational change. In
contrast to the RasGAP mechanism, an accumulation of a state in which phosphate
is bound is not observed, and bond breakage is the rate-limiting step. The
movement of trans-glutamine and trans-arginine into the catalytic site and bond
breakage during hydrolysis are monitored in real time. The combination of X-ray
structure analysis and time-resolved FTIR spectroscopy provides detailed insight
in the catalysis of human Rab GTPases.
|
|
|
|
|
|
|
