Crystal Structures of the Organomercurial Lyase MerB in Its Free and Mercury-bound Forms: INSIGHTS INTO THE MECHANISM OF METHYLMERCURY DEGRADATION

Journal Article · Tue Jan 27 04:00:00 EST 2009 · J. Biol. Chem.

DOI:https://doi.org/10.1074/jbc.M807143200· OSTI ID:1018551

Lafrance-Vanasse, Julien; Lefebvre, Maryse; Lello, Paola Di; Sygusch, Jurgen; Omichinski, James G ^[1]

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1. (Montreal)

Bacteria resistant to methylmercury utilize two enzymes (MerA and MerB) to degrade methylmercury to the less toxic elemental mercury. The crucial step is the cleavage of the carbon-mercury bond of methylmercury by the organomercurial lyase (MerB). In this study, we determined high resolution crystal structures of MerB in both the free (1.76-{angstrom} resolution) and mercury-bound (1.64-{angstrom} resolution) states. The crystal structure of free MerB is very similar to the NMR structure, but important differences are observed when comparing the two structures. In the crystal structure, an amino-terminal {alpha}-helix that is not present in the NMR structure makes contact with the core region adjacent to the catalytic site. This interaction between the amino-terminal helix and the core serves to bury the active site of MerB. The crystal structures also provide detailed insights into the mechanism of carbon-mercury bond cleavage by MerB. The structures demonstrate that two conserved cysteines (Cys-96 and Cys-159) play a role in substrate binding, carbon-mercury bond cleavage, and controlled product (ionic mercury) release. In addition, the structures establish that an aspartic acid (Asp-99) in the active site plays a crucial role in the proton transfer step required for the cleavage of the carbon-mercury bond. These findings are an important step in understanding the mechanism of carbon-mercury bond cleavage by MerB.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE Office of Science (SC)
• OSTI ID: 1018551
• Journal Information: J. Biol. Chem., Journal Name: J. Biol. Chem. Journal Issue: (2) ; 01, 2009 Vol. 284; ISSN JBCHA3; ISSN 0021-9258
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ASPARTIC ACID
BACTERIA
CLEAVAGE
CRYSTAL STRUCTURE
ENZYMES
LYASES
MERCURY
METHYLMERCURY
PROTONS
RESOLUTION
SUBSTRATES