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Crossover inhibition as an indicator of convergent evolution of enzyme mechanisms: A β‐lactamase and a N‐terminal nucleophile hydrolase
Author(s) -
Adediran S.A.,
Lin G.,
Pelto R.B.,
Pratt R.F.
Publication year - 2012
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.2012.10.019
Subject(s) - amidohydrolase , hydrolase , active site , enzyme , nucleophile , chemistry , stereochemistry , covalent bond , biochemistry , protease , proteasome , catalysis , organic chemistry
O ‐Aryloxycarbonyl hydroxamates and 1,3,4‐oxathiazol‐2‐ones have been identified as covalent inhibitors of β‐lactamases and proteasomes, respectively. The products of these inhibition reactions are remarkably similar, involving carbonyl cross‐linking of the active sites. We have cross‐checked these inhibitors, showing that the former inhibit proteasomes and the latter β‐lactamases, to form the same inactive carbonyl adducts. These results are discussed in terms of similarities of the active site structures and catalytic mechanisms. It is likely that a mechanistic imperative has led to convergent evolution of these enzyme active sites, of a β‐lactam‐recognizing enzyme and a N‐terminal protease belonging to different amidohydrolase superfamilies.