PHOSPHATASES 441 



relative binding energies are shown in Table 2-25. It was assumed that ( + )- 

 tartrate is bound to the enzyme at four points; the two carboxylate groups 

 interact with two enzyme cationic groups and the two hydroxyl groups 



Table 2-25 

 Competitive Anionic Inhibitors or Prostatic Phosphatase" 



Inhibitor 



Fluoride dimer (HF^ 



( + )-Tartrate 



DL-Glycerate 



meso-Tartrate 



Arsenate 



D-Malate 



Sulfamate 



Nitrate 



D- Alanine 



L-Leucine 



Diphenylphosphate 



D-Lactate 



L-Serine 



L-Glutamate 



L-Aspartate 



( — )-Tartrate 



L- Lactate 



L-Malate 



L- Alanine 



Glycine 



" The substrate is /S-glycerophosphate {K,^ — 16 mM). Experiments with amino 

 acids at pH 7.2 and with the rest at pH 5. (From London et al., 1958.) 



" Kj for D-malate estimated from value for DL-malate since L-malate is a weak in- 

 hibitor. 



form hydrogen bonds with the enzyme (Fig. 2-14). On the basis of this 

 model it is possible to explain most of the variations in inhibitor binding. 

 ( — )-Tartrate can make contact at only two points while meso-tartrate can 

 make a three-point attachment in two ways. Only D-malate can attach at 

 three points like ( + ) -tartrate but the second hydroxyl group is missing. 

 The most important requirement for binding is a negative group separated 

 from the nucleophilic group by around 2.9 A. (-f )-Tartrate has two such 

 units. In the substrates the oxygen atom of phosphate is the nucleophilic 

 atom. The amino acids are rather poor inhibitors, probably because at 



