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Crystal structure of the tellurite detoxification protein TehB from E. coli in complex with SAH
Structural highlights
FunctionTEHB_ECOLI S-adenosyl-L-methionine dependent methyltransferase that catalyzes the methylation of tellurite and is responsible for tellurite resistance when present in high copy number. Can also methylate selenite and selenium dioxide. Is thus able to detoxify different chalcogens. Can not methylate arsenic compounds.[1] [2] Publication Abstract from PubMedThe oxyanion derivatives of the chalcogens tellurium and selenium are toxic to living organisms even at very low levels. Bacteria have developed mechanisms to overcome their toxicity by methylating them. The structure of the TehB from Escherichia coli has been determined in the presence of the co-factor analogues S-adenosyl-homocysteine (SAH) and sinefungin (non-hydrolysable form of S-adenosyl-L-methionine) at 1.48 A and 1.9 A respectively. Interestingly, our kinetic data show that TehB does not discriminate between selenium or tellurite oxyanions, making it a very powerful detoxifying protein. Analysis of the active site has identified three conserved residues that are capable of binding and orientating the metals for nucleophilic attack, His176, Arg177 and Arg184. Mutagenesis studies revealed that the His176Ala and Arg184Ala mutants retained most of their activity, whereas the Arg177Ala mutant had 65 % of its activity abolished. Based on the structure and kinetic data we propose an SN2 nucleophilic attack reaction mechanism. These data provide the first molecular understanding on the detoxification of chalcogens by bacteria. Structure and mechanism of the chalcogen detoxifying protein TehB from Escherichia coli.,Choudhury HG, Cameron AD, Iwata S, Beis K Biochem J. 2011 Jan 18. PMID:21244361[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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