Hydrolytic metallo-enzymes

Uncovering of the three dimentional structure of catalytic groups at the active site of an enzyme allows to theorize the catalytic mechanism, and the theory accelerates the designing of model systems. Examples of such enzymes are zinc ion containing carboxypeptidase A 1-5) and carbonic anhydrase6-11. There are many other zinc enzymes with a variety of catalytic functions. For example, alcohol dehydrogenase is also a zinc enzyme and the subject of intensive model studies. However, the topics of this review will be confined to the model studies of the former hydrolytic metallo-enzymes. 

Molenveld P et al (1999) Dinuclear and trinuclear Zn(II) calix[4]arene complexes as models for hydrolytic metallo-enzymes. Synthesis and catalytic activity in phosphate diester transesterification. J Org Chem 64 3896-3906... 

Metallomicelles made up of ligand surfactants and bound metal ions have been studied extensively as artificial hydrolytic metallo-enzymes. Many such systems have become large and complex, but a study of a simple (1 1) Co(II) complex with triethanolamine showed that in the presence of CTAB or Triton X-100, it could catalyse PNPP (67) hydrolysis at pH 7 with a rate enhancement factor of 1000-fold. " ... 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

Classification of this enzyme as a serine, cysteine, aspartic, or metallo-dependent enzyme [50] is somewhat problematic because occasionally inhibitors from the same class led to contradictory results. The observed effects suggest, however, that both metal ions and sulfhydryl groups may play a major role in the hydrolytic mechanism. Therefore, most probably the enzyme is a metallocysteine hydrolase. 

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