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The Bacillus anthracis arylamine N ‐acetyltransferase ((BACAN)NAT1) that inactivates sulfamethoxazole, reveals unusual structural features compared with the other NAT isoenzymes
Author(s) -
Pluvinage Benjamin,
Li de la Sierra-Gallay In's,
Kubiak Xavier,
Xu Ximing,
Dairou Julien,
Dupret Jean-Marie,
Rodrigues-Lima Fernando
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.10.041
Subject(s) - bacillus anthracis , nat , arylamine n acetyltransferase , acetyltransferases , acetyltransferase , cofactor , enzyme , biochemistry , acetylation , chemistry , isozyme , biology , stereochemistry , bacteria , genetics , gene , computer network , computer science
Arylamine N ‐acetyltransferases (NATs) are xenobiotic‐metabolizing enzymes that biotransform arylamine drugs. The Bacillus anthracis (BACAN)NAT1 enzyme affords increased resistance to the antibiotic sulfamethoxazole through its acetylation. We report the structure of (BACAN)NAT1. Unexpectedly, endogenous coenzymeA was present in the active site. The structure suggests that, contrary to the other prokaryotic NATs, (BACAN)NAT1 possesses a 14‐residue insertion equivalent to the “mammalian insertion”, a structural feature considered unique to mammalian NATs. Moreover, (BACAN)NAT1 structure shows marked differences in the mode of binding and location of coenzymeA when compared to the other NATs. This suggests that the mechanisms of cofactor recognition by NATs is more diverse than expected and supports the cofactor‐binding site as being a unique subsite to target in drug design against bacterial NATs.