Bulgecin A: a novel inhibitor of binuclear metallo-beta-lactamases

AM Simm, EJ Loveridge, J Crosby, MB Avison, TR Walsh, PM Bennett

Research output: Contribution to journalArticle (Academic Journal)peer-review

32 Citations (Scopus)


Bulgecin A, a sulphonated N-acetyl-D-glucosamine unit linked to a 4-hydroxy-5-hydroxymethylproline ring by a beta-glycosidic linkage, is a novel type of inhibitor for binuclear metallo-beta-lactamases. Using steady-state kinetic analysis with nitrocefin as the beta-lactam substrate, bulgecin A competitively inhibited the metallo-beta-lactamase BceII from Bacillus cereus in its two-zinc form, but failed to inhibit when the enzyme was in the single-zinc form. The competitive inhibition was restored by restoring the second zinc ion. The single-zinc metallo-beta-lactamase from Aeromonas veronii bv. sobria, ImiS, was not inhibited by bulgecin A. The tetrameric L1 metallo-beta-lactamase from Stenotrophomonas maltophilia was subject to partial non-competitive inhibition, which is consistent with a kinetic model in which the enzyme bound to inhibitor retains catalytic activity. Docking experiments support the conclusion that bulgecin A co-ordinates to the zinc II site in metallo-beta-lactamases via the terminal sulphonate group on the sugar moiety.
Translated title of the contributionBulgecin A: a novel inhibitor of binuclear metallo-beta-lactamases
Original languageEnglish
Pages (from-to)585 - 590
Number of pages6
JournalBiochemical Journal
Publication statusPublished - May 2005

Bibliographical note

Publisher: The Biochemical Society


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