Mock, Matthew

The collapse of the proteolytic tetrahedral intermediate of the promoted-water pathway requires a proton donor in order to facilitate the departure of the leaving amino group. Rees and Lipscomb (1982) considered Glu-270, but favored Tyr-248 for this role, but Monzingo and Matthews (1984) fully elaborated on a role for Glu-270 of carboxypeptidase A and Glu-143 of thermolysin as intermediate proton donors. This proposal for carboxypeptidase A is corroborated by the near-normal activity observed for the Tyr-248- Phe mutant of rat carboxypeptidase A (Garden et al, 1985 Hilvert et al, 1986) and is reflected in the mechanistic scheme of Fig. 31 (Christianson and Lipscomb, 1989). Mock (1975) considered Glu-270 a proton donor in the carboxypeptidase A mechanism, but his mechanism does not favor a Glu-270/zinc-promoted water molecule as the hydrolytic nucleophile. Schepartz and Breslow (1987) observed that Glu-270 may mediate an additional proton transfer in the generation of the Pi product carboxylate. 

Pindolia, K., Jordan, M., Guo, C., Matthews, N., Mock, D.M., Strovel, E., Blitzer, M., and Wolf, B., 2011. Development and characterization of a mouse with profound biotinidase deficiency a biotin-responsive neurocuta-neous disorder. Molecular Genetics and Metabolism. 102 161-169. 

Stratton, S.L., Horvath, T.D., Bogusiewicz, A., Matthews, N.I., Henrich, C.L., Spencer, H.J., Moran, J.H., and Mock, D.M., 2011. Urinary excretion of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans. The Journal of Nutrition. 141 353-358. 

MATTHEW R. MOCK Department of Health and Hiunan Services, Berkeley Mental Health, Family, Youth, and Children s Services, Berkeley, California 94704. 

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