Mercury Detoxification by Bacteria: Simulations of Transcription Activation and MercuryCarbon Bond Cleavage

Abstract

Hao-Bo Guo, Jerry M. Parks, Alexander Johs, and Jeremy C. Smith20.1IntroductionMercury,aheavyelementthatiswidelydistributedthroughoutthebiosphere,isquitereactive, being susceptible to redox, photochemical, and various other chemicaltransformations.However,mercuryhasnoknownbeneficialbiologicalfunction,andis toxic to living organisms in all chemical forms.Mercury toxicity derives from its extremely high affinity for sulfur-containingligands such as cysteine and glutathione. Monomethylmercury, or simply methyl-mercury, is particularly toxic due to its extremely high thiolate affinity, its ability tocrosstheplacentalandblood–brainbarriers,anditspropensityforbioaccumulationin living organisms [1].Many bacteria that live in mercury-polluted environments possess a fascinatingsuiteofgenescalledthemercuryresistance,ormer,operon,whichencodesasetofproteins and enzymes that convert inorganic and organomercurial species tovolatile,lesstoxicelementalHg(0)[1,2].Themeroperonisencodedinplasmidsortransposons, and can be transferred to other organisms via horizontal genetransfer.Several proteins and enzymes are encoded by the mer operon. These include theperiplasmicHgtransporter,MerP, membrane-bound proteinssuchas MerC,MerT,and others, and the mercuric reductase, MerA. Broad-spectrum mercury-resistantorganisms also encode an organomercurial lyase, MerB, which is responsible fordegrading organomercury compounds such as methylmercury.Transcription of theGram-negative mer operon is regulated by MerR.In this chapter are described the results of recent investigations [3, 4] on thetranscriptional regulator, MerR, and the organomercurial lyase, MerB. First, acombined experimental and computational approach is detailed in which small-angle X-ray scattering (SAXS) experiments and molecular dynamics (MD) simula-tionswereusedtoprobethestructureanddynamicsofthetranscriptionalregulatorMerR. MD simulations have revealed the principal conformational changes inMerRuponHg(II)-binding,whichprovidesinsightintothemolecularmechanism