Paper Citing NAMD - Abstract
Gao, Yang; Iancu, Cristina V.; Mukind, Susmith; Choe, Jun-Yong; Honzatko, Richard B.
Mechanism of Displacement of a Catalytically Essential Loop from the Active Site of Mammalian Fructose-1,6-bisphosphatase
BIOCHEMISTRY, 52:5206-5216, AUG 6 2013
AMP triggers a 15 degrees 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/Mg2+ and AMP/Zn2+ complexes of Asp(10) FBPase are in intermediate quaternary conformations (completing 12 degrees of the subunit-pair rotation), but the complex with Zn2+ provides the first instance of an engaged loop in a near-T quaternary state. The 12 degrees 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 degrees 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.
