1YXI: R-State AMP Complex Reveals Initial Steps of the Quaternary Transition of Fructose-1,6-bisphosphatase

Citation:
Abstract
AMP transforms fructose-1,6-bisphosphatase from its active R-state to its inactive T-state; however, the mechanism of that transformation is poorly understood. The mutation of Ala(54) to leucine destabilizes the T-state of fructose-1,6-bisphosphatase. The mutant enzyme retains wild-type levels of activity, but the concentration of AMP that causes 50% inhibition increases 50-fold. In the absence of AMP, the Leu(54) enzyme adopts an R-state conformation nearly identical to that of the wild-type enzyme. The mutant enzyme, however, grows in two crystal forms in the presence of saturating AMP. In one form, the AMP-bound tetramer is in a T-like conformation, whereas in the other form, the AMP-bound tetramer is in a R-like conformation. The latter reveals conformational changes in two helices due to the binding of AMP. Helix H1 moves toward the center of the tetramer and displaces Ile(10) from a hydrophobic pocket. The displacement of Ile(10) exposes a hydrophobic surface critical to interactions that stabilize the T-state. Helix H2 moves away from the center of the tetramer, breaking hydrogen bonds with a buried loop (residues 187-195) in an adjacent subunit. The same hydrogen bonds reform but only after the quaternary transition to the T-state. Proposed here is a model that accounts for the quaternary transition and cooperativity in the inhibition of catalysis by AMP.
PDB ID: 1YXIDownload
MMDB ID: 32583
PDB Deposition Date: 2005/2/21
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 1YXI: tetrameric; determined by author and by software (PISA,PQS)
Molecular Components in 1YXI
Label Count Molecule
Proteins (4 molecules)
4
Fructose-1,6-bisphosphatase(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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