PDBsum entry 2f3d

Hydrolase

PDB id: 2f3d

Contents

Protein chain

328 a.a. *

Ligands

F6P

PO4

AMP

Metals

_ZN ×3

Waters ×181

* Residue conservation analysis

PDB id:

2f3d

Name:

Hydrolase

Title:

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

Structure:

Fructose-1,6-bisphosphatase 1. Chain: a. Synonym: d-fructose-1,6-bisphosphate 1-phosphohydrolase 1, fbpase 1. Engineered: yes. Mutation: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Gene: fbp1, fbp. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.83Å R-factor: 0.222 R-free: 0.246

Authors:

C.V.Iancu,S.Mukund,J.-Y.Choe,H.J.Fromm,R.B.Honzatko

Key ref:

Y.Gao et al. (2013). Mechanism of displacement of a catalytically essential loop from the active site of mammalian fructose-1,6-bisphosphatase. Biochemistry, 52, 5206-5216. PubMed id: 23844654 DOI: 10.1021/bi400532n

Date:

21-Nov-05 Release date: 25-Apr-06

Protein chain

P00636  (F16P1_PIG) -  Fructose-1,6-bisphosphatase 1 from Sus scrofa

Seq: 338 a.a.

Struc: 328 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.3.11 - fructose-bisphosphatase.
• Pathway: Pentose Phosphate Pathway (later stages)
• Reaction: beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate

beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-phosphate (Bound ligand (Het Group name = F6P) corresponds exactly) + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi400532n

Biochemistry 52:5206-5216 (2013)

PubMed id: 23844654

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

Y.Gao, C.V.Iancu, S.Mukind, J.Y.Choe, R.B.Honzatko.

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.