 |
PDBsum entry 2f3d
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Mechanism of displacement of a catalytically essential loop from the active site of mammalian fructose-1,6-Bisphosphatase.
|
|
|
Authors
|
|
Y.Gao,
C.V.Iancu,
S.Mukind,
J.Y.Choe,
R.B.Honzatko.
|
|
|
Ref.
|
|
Biochemistry, 2013,
52,
5206-5216.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
AMP triggers a 15° subunit-pair rotation in fructose-1,6-bisphosphatase
(FBPase) from its active R state to its inactive T state. During this
transition, a catalytically essential loop (residues 50-72) leaves its active
(engaged) conformation. Here, the structures of Ile(10) → Asp FBPase and
molecular dynamic simulations reveal factors responsible for loop displacement.
The AMP/Mg(2+) and AMP/Zn(2+) complexes of Asp(10) FBPase are in intermediate
quaternary conformations (completing 12° of the subunit-pair rotation), but the
complex with Zn(2+) provides the first instance of an engaged loop in a near-T
quaternary state. The 12° subunit-pair rotation generates close contacts
involving the hinges (residues 50-57) and hairpin turns (residues 58-72) of the
engaged loops. Additional subunit-pair rotation toward the T state would make
such contacts unfavorable, presumably causing displacement of the loop. Targeted
molecular dynamics simulations reveal no steric barriers to subunit-pair
rotations of up to 14° followed by the displacement of the loop from the active
site. Principal component analysis reveals high-amplitude motions that
exacerbate steric clashes of engaged loops in the near-T state. The results of
the simulations and crystal structures are in agreement: subunit-pair rotations
just short of the canonical T state coupled with high-amplitude modes sterically
displace the dynamic loop from the active site.
|
|
|
|
|
|
|
