7TXG

Structure of the Class II Fructose-1,6-Bisphosphatase from Francisella tularensis with native Mn++ divalent cation and partially occupied product F6P

Summary for 7TXG

• Entry DOI: 10.2210/pdb7txg/pdb
• Descriptor: Fructose-1,6-bisphosphatase, GLYCEROL, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: class ii fbpases; fructose-1, 6-bisphosphatase; francisella tularensis; mycobacterium tuberculosis; gluconeogenesis; antibiotic targets, hydrolase
• Biological source: Francisella tularensis
• Total number of polymer chains: 4
• Total formula weight: 149629.95

Authors

Abad-Zapatero, C.,Selezneva, A.I.,Harding, L.N.M.,Movahedzadeh, F. (deposition date: 2022-02-09, release date: 2023-06-28, Last modification date: 2023-10-25)

Primary citation

Selezneva, A.I.,Harding, L.N.M.,Gutka, H.J.,Movahedzadeh, F.,Abad-Zapatero, C.
New structures of Class II Fructose-1,6-Bisphosphatase from Francisella tularensis provide a framework for a novel catalytic mechanism for the entire class.
Plos One, 18:e0274723-e0274723, 2023

PubMed Abstract: Class II Fructose-1,6-bisphosphatases (FBPaseII) (EC: 3.1.3.11) are highly conserved essential enzymes in the gluconeogenic pathway of microorganisms. Previous crystallographic studies of FBPasesII provided insights into various inactivated states of the enzyme in different species. Presented here is the first crystal structure of FBPaseII in an active state, solved for the enzyme from Francisella tularensis (FtFBPaseII), containing native metal cofactor Mn2+ and complexed with catalytic product fructose-6-phosphate (F6P). Another crystal structure of the same enzyme complex is presented in the inactivated state due to the structural changes introduced by crystal packing. Analysis of the interatomic distances among the substrate, product, and divalent metal cations in the catalytic centers of the enzyme led to a revision of the catalytic mechanism suggested previously for class II FBPases. We propose that phosphate-1 is cleaved from the substrate fructose-1,6-bisphosphate (F1,6BP) by T89 in a proximal α-helix backbone (G88-T89-T90-I91-T92-S93-K94) in which the substrate transition state is stabilized by the positive dipole of the 〈-helix backbone. Once cleaved a water molecule found in the active site liberates the inorganic phosphate from T89 completing the catalytic mechanism. Additionally, a crystal structure of Mycobacterium tuberculosis FBPaseII (MtFBPaseII) containing a bound F1,6BP is presented to further support the substrate binding and novel catalytic mechanism suggested for this class of enzymes.

PubMed: 37352301
DOI: 10.1371/journal.pone.0274723

Experimental method

X-RAY DIFFRACTION (1.9 Å)