2F3B: Mechanism Of Displacement Of A Catalytically Essential Loop From The Active Site Of Fructose-1,6-bisphosphatase

Citation:
Abstract
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/Mg(2+) and AMP/Zn(2+) complexes of Asp(10) FBPase are in intermediate quaternary conformations (completing 12 degrees 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 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.
PDB ID: 2F3BDownload
MMDB ID: 38696
PDB Deposition Date: 2005/11/20
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2F3B: tetrameric; determined by author and by software (PISA,PQS)
Molecular Components in 2F3B
Label Count Molecule
Proteins (4 molecules)
4
Fructose-1,6-bisphosphatase 1(Gene symbol: FBP1)
Molecule annotation
Chemicals (24 molecules)
1
4
2
8
3
12
* Click molecule labels to explore molecular sequence information.

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