Inhibition of Family II Pyrophosphatases by Analogs of Pyrophosphate and Phosphate

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A. B. Zyryanov¹, R. Lahti², and A. A. Baykov^1*

¹Belozersky Institute of Physico-Chemical Biology and Faculty of Chemistry, Lomonosov Moscow State University, 119899 Moscow, Russia; fax: (7-095) 939-3181; E-mail: baykov@genebee.msu.su

²Department of Biochemistry and Food Chemistry, University of Turku, Turku, FIN-20500, Finland; fax: (358-2) 633-6860; E-mail: reijo.lahti@utu.fi

^* To whom correspondence should be addressed.

Received November 1, 2004

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Imidodiphosphate (the pyrophosphate analog containing a nitrogen atom in the bridge position instead of oxygen) is a potent inhibitor of family II pyrophosphatases from Streptococcus mutans and Streptococcus gordonii (inhibition constant K_i ~ 10 µM), which is slowly hydrolyzed by these enzymes with a catalytic constant of ~1 min^-1. Diphosphonates with different substituents at the bridge carbon atom are much less effective (K_i = 1-6 mM). The value of K_i for sulfate (a phosphate analog) is only 12 mM. The inhibitory effect of the pyrophosphate analogs exhibits only a weak dependence on the nature of the metal ion (Mn, Mg, or Co) bound in the active site.

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KEY WORDS: pyrophosphatase, diphosphonate, phosphate, inhibition, family II, Streptococcus mutans, Streptococcus gordonii

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