2F3D

Mechanism of displacement of a catalytically essential loop from the active site of fructose-1,6-bisphosphatase

Summary for 2F3D

• Entry DOI: 10.2210/pdb2f3d/pdb
• Related: 1CNQ 1EYI 1Q9D 1YXI 1YYZ 1YZO 2F3B 2F3H
• Descriptor: Fructose-1,6-bisphosphatase 1, 6-O-phosphono-beta-D-fructofuranose, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: allosteric regulation, allostery, fructose-1, 6-bisphosphatase, fbpase, enzyme catalysis, loop displacement, hydrolase
• Biological source: Sus scrofa (pig)
• Total number of polymer chains: 1
• Total formula weight: 37722.89

Authors

Iancu, C.V.,Mukund, S.,Choe, J.-Y.,Fromm, H.J.,Honzatko, R.B. (deposition date: 2005-11-21, release date: 2006-04-25, Last modification date: 2024-02-14)

Primary citation

Gao, Y.,Iancu, C.V.,Mukind, S.,Choe, J.Y.,Honzatko, R.B.
Mechanism of displacement of a catalytically essential loop from the active site of mammalian fructose-1,6-bisphosphatase.
Biochemistry, 52:5206-5216, 2013

PubMed 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.

PubMed: 23844654
DOI: 10.1021/bi400532n

Experimental method

X-RAY DIFFRACTION (1.83 Å)