NMR Structural Studies Reveal a Novel Protein Fold for Merb, the Organomercurial Lyase Involved in the Bacterial Mercury Resistance System

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Abstract

Mercury resistant bacteria have developed a system of two enzymes (MerA and MerB), which allows them to efficiently detoxify both ionic and organomercurial compounds. The organomercurial lyase (MerB) catalyzes the protonolysis of the carbon-mercury bond resulting in the formation of ionic mercury and a reduced hydrocarbon. The ionic mercury [Hg(II)] is subsequently reduced to the less reactive elemental mercury [Hg(0)] by a specific mercuric reductase (MerA). To better understand MerB's unique enzymatic activity, we used nuclear magnetic resonance (NMR) spectroscopy to determine the structure of the free enzyme. MerB is characterized by a novel protein fold consisting of three noninteracting antiparallel beta-sheets surrounded by six alpha-helices. By comparing the NMR data of free MerB and the MerB/Hg/DTT complex, we identified a set of residues that likely define a Hg/DTT binding site. These residues cluster around two cysteines (C(96) and C(159)) that are crucial to MerB's catalytic activity. A detailed analysis of the structure revealed the presence of an extensive hydrophobic groove adjacent to this Hg/DTT binding site. This extensive hydrophobic groove has the potential to interact with the hydrocarbon moiety of a wide variety of substrates and may explain the broad substrate specificity of MerB.

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© Biochemistry 2004, American Chemical Society

Di Lello, P., Benison, G., Valafar, H., Pitts, K., Summers, A., Legault, P., & Omichinski, J. (2004). NMR Structural Studies Reveal a Novel Protein Fold for MerB, the Organomercurial Lyase Involved in the Bacterial Mercury Resistance System†,‡. Biochemistry, 43(26), 8322-8332. doi: 10.1021/bi049669z

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