Inhibition of family II pyrophosphatases by analogs of pyrophosphate and phosphate.
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 Ki approximately 10 microM), which is slowly hydrolyzed by these enzymes with a catalytic constant of approximately 1 min(-1). Diphosphonates with different substituents at the bridge carbon atom are much less effective (Ki = 1-6 mM). The value of Ki 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.
Zyryanov
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Belozersky Institute of Physico-Chemical Biology and Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119899, Russia. baykov@genebee.msu.su
Lahti
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Baykov
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D003035:Cobalt / Q000737:chemistry; D011756:Diphosphates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004164:Diphosphonates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry; D008345:Manganese / Q000737:chemistry; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D013291:Streptococcus / Q000201:enzymology; D013295:Streptococcus mutans / Q000201:enzymology; D013379:Substrate Specificity
D011756:Diphosphates; D004164:Diphosphonates; D010710:Phosphates; C016514:imidodiphosphonic acid; D003035:Cobalt; D008345:Manganese; D011755:Pyrophosphatases; D008274:Magnesium