Professionals Urge End to Water Fluoridation

Below abstract indicates fluoride derivative inhibits mito function in
cows.

Structure of bovine mitochondrial F(1)-ATPase inhibited by Mg(2+) ADP
and aluminium fluoride.

BACKGROUND: The globular domain of the membrane-associated F(1)F(o)-
ATP synthase complex can be detached intact as a water-soluble
fragment known as F(1)-ATPase. It consists of five different subunits,
alpha, beta, gamma, delta and epsilon, assembled with the
stoichiometry 3:3:1:1:1. In the crystal structure of bovine F(1)-
ATPase determined previously at 2.8 A resolution, the three catalytic
beta subunits and the three noncatalytic alpha subunits are arranged
alternately around a central alpha-helical coiled coil in the gamma
subunit. In the crystals, the catalytic sites have different
nucleotide occupancies. One contains the triphosphate form of the
nucleotide, the second contains the diphosphate, and the third is
unoccupied. Fluoroaluminate complexes have been shown to mimic the
transition state in several ATP and GTP hydrolases. In order to
understand more about its catalytic mechanism, F(1)-ATPase was
inhibited with Mg(2+)ADP and aluminium fluoride and the structure of
the inhibited complex was determined by X-ray crystallography.
RESULTS: The structure of bovine F(1)-ATPase inhibited with Mg(2+)ADP
and aluminium fluoride determined at 2.5 A resolution differs little
from the original structure with bound AMP-PNP and ADP. The nucleotide
occupancies of the alpha and beta subunits are unchanged except that
both aluminium trifluoride and Mg(2+)ADP are bound in the nucleotide-
binding site of the beta(DP) subunit. The presence of aluminium
fluoride is accompanied by only minor adjustments in the surrounding
protein. CONCLUSIONS: The structure appears to mimic a possible
transition state. The coordination of the aluminofluoride group has
many features in common with other aluminofluoride-NTP hydrolase
complexes. Apparently, once nucleotide is bound to the catalytic beta
subunit, no additional major structural changes are required for
catalysis to occur. PMID: 10873854