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NMR structural studies reveal a novel protein fold for MerB, the organomercurial lyase involved in the bacterial mercury resistance system.

Di Lello P, Benison GC, Valafar H, Pitts KE, Summers AO, Legault P, Omichinski JG
Biochemistry 43 8322-32 (2004)
Cited: 15 times
EuropePMC logo PMID: 15222745

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.

Reviews citing this publication (3)

  1. A bacterial view of the periodic table: genes and proteins for toxic inorganic ions. Silver S, Phung le T. J. Ind. Microbiol. Biotechnol. 32 587-605 (2005)
  2. Mercury-alkyl bond cleavage based on organomercury lyase. Strasdeit H. Angew. Chem. Int. Ed. Engl. 47 828-830 (2008)
  3. Demethylation-The Other Side of the Mercury Methylation Coin: A Critical Review. Barkay T, Gu B. ACS Environ Au 2 77-97 (2022)

Articles citing this publication (12)

  1. Improved disorder prediction by combination of orthogonal approaches. Schlessinger A, Punta M, Yachdav G, Kajan L, Rost B. PLoS ONE 4 e4433 (2009)
  2. Cleaving mercury-alkyl bonds: a functional model for mercury detoxification by MerB. Melnick JG, Parkin G. Science 317 225-227 (2007)
  3. In silico identification of putative metal binding motifs. Thilakaraj R, Raghunathan K, Anishetty S, Pennathur G. Bioinformatics 23 267-271 (2007)
  4. Direct measurement of mercury(II) removal from organomercurial lyase (MerB) by tryptophan fluorescence: NmerA domain of coevolved γ-proteobacterial mercuric ion reductase (MerA) is more efficient than MerA catalytic core or glutathione . Hong B, Nauss R, Harwood IM, Miller SM. Biochemistry 49 8187-8196 (2010)
  5. New insights into the metabolism of organomercury compounds: mercury-containing cysteine S-conjugates are substrates of human glutamine transaminase K and potent inactivators of cystathionine γ-lyase. Bridges CC, Krasnikov BF, Joshee L, Pinto JT, Hallen A, Li J, Zalups RK, Cooper AJ. Arch. Biochem. Biophys. 517 20-29 (2012)
  6. News Cleaving C-Hg bonds: two thiolates are better than one. Miller SM. Nat. Chem. Biol. 3 537-538 (2007)
  7. DFT studies of the degradation mechanism of methyl mercury activated by a sulfur-rich ligand. Li X, Liao RZ, Zhou W, Chen G. Phys Chem Chem Phys 12 3961-3971 (2010)
  8. Expanded Diversity and Phylogeny of mer Genes Broadens Mercury Resistance Paradigms and Reveals an Origin for MerA Among Thermophilic Archaea. Christakis CA, Barkay T, Boyd ES. Front Microbiol 12 682605 (2021)
  9. Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon-Metal Bond Cleavage. Wahba HM, Stevenson MJ, Mansour A, Sygusch J, Wilcox DE, Omichinski JG. J. Am. Chem. Soc. 139 910-921 (2017)
  10. Characterization of three rapidly growing novel Mycobacterium species with significant polycyclic aromatic hydrocarbon bioremediation potential. Deng Y, Mou T, Wang J, Su J, Yan Y, Zhang YQ. Front Microbiol 14 1225746 (2023)
  11. Dimethylmercury Degradation by Dissolved Sulfide and Mackinawite. West J, Graham AM, Liem-Nguyen V, Jonsson S. Environ Sci Technol 54 13731-13738 (2020)
  12. Mechanistic pathways of mercury removal from the organomercurial lyase active site. Silva PJ, Rodrigues V. PeerJ 3 e1127 (2015)


Related citations provided by authors (1)

  1. 1H, 15N, and 13C resonance assignment of the 23 kDa organomercurial lyase MerB in its free and mercury-bound forms.. Di Lello P, Benison GC, Omichinski JG, Legault P J Biomol NMR 29 457-8 (2004)

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