Simm, Alan M., Loveridge, Edric Joel, Crosby, John, Avison, Matthew B., Walsh, Timothy Rutland ORCID: https://orcid.org/0000-0003-4315-4096 and Bennett, Peter M. 2005. Bulgecin A: a novel inhibitor of binuclear metallo-beta-lactamases. Biochemical Journal 387 (3) , pp. 585-590. 10.1042/BJ20041542 |
Abstract
Bulgecin A, a sulphonated N-acetyl-D-glucosamine unit linked to a 4-hydroxy-5-hydroxymethylproline ring by a b-glycosidic linkage, is a novel type of inhibitor for binuclear metallo-b-lactamases. Using steady-state kinetic analysis with nitrocefin as the b-lactam substrate, bulgecin A competitively inhibited the metallo-b-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-b-lactamase from Aeromonas veronii bv. sobria, ImiS, was not inhibited by bulgecin A. The tetrameric L1 metallo-b-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-b-lactamases via the terminal sulphonate group on the sugar moiety.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences Chemistry Medicine Systems Immunity Research Institute (SIURI) |
Subjects: | R Medicine > R Medicine (General) |
Uncontrolled Keywords: | antibiotic resistance; bulgecin A; inhibitor; metallo-b-lactamase; Stenotrophomonas; zinc co-ordination. |
ISSN: | 1470-8728 |
Last Modified: | 17 Oct 2022 08:30 |
URI: | https://orca.cardiff.ac.uk/id/eprint/308 |
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