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Structure and mechanism of the chalcogen detoxifying protein TehB from Escherichia coli

DOI: 10.1042/BJ20102014 DOI Help
PMID: 21244361 PMID Help

Authors: Hassan Choudhury (Imperial College London) , Alex Cameron (Imperial College London) , So Iwata (Diamond Light Source) , Konstantinos Beis (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemical Journal

State: Published (Approved)
Published: January 2011

Abstract: The 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 Å and 1.9 Å 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.

Journal Keywords: Biocatalysis; Catalytic; Chalcogens; Consensus; Crystallography; X-Ray; Drug; Bacterial; Escherichia; Kinetics; Methylation; Mutagenesis; Site-Directed; Mutant; Organoselenium; Protein; Recombinant; S-Adenosylhomocysteine; Sequence; Sequence; Amino; Tellurium

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography