Transition Metal Cation Inhibition of Mycobacterium tuberculosis Esterase Rv0045c

Abstract

The survival of Mycobacterium tuberculosis within its human host is highly dependent upon the lipid metabolism performed by the numerous serine hydrolase enzymes at the bacterium's disposal. Among these serine hydrolases, Rv0045c is a mycobacterial‐specific serine hydrolase that has been characterized for global substrate specificity by scanning the hydrolase against a library of fluorogenic hydrolase substrates. Rv0045c expresses strong selectivity for short, straight‐chained alkyl esters, but the relative enzyme kinetic rate is slow in comparison to a majority of bacterial hydrolases. Herein, we determined the transition metal ion dependence of Rv0045c on hydrolysis of the four‐carbon methoxyacetic fluorogenic substrate. The catalytic activity of Rv0045c was significantly inhibited by low concentrations of Ni+2, Cu+2, and Zn+2 metal cations while other 3d metal cations displayed no effects on the activity of the hydrolase. The low inhibition constants for these three metals on Rv0045c suggest a likely physiological relevance for the metal dependent inhibition of Rv0045c.Support or Funding InformationFunding provided by a Butler University Holcomb research award and a Senior Research Grant from the Indiana Academy of Sciences.