A BIFUNCTIONAL MONOCYCLIC BETA-LACTAM CROSS-LINKS ACROSS THE ACTIVE-SITE OF BETA-LACTAMASE

A 4-alkoxy-2-azetidinone behaves as a bifunctional active site-directe d inhibitor of the class A beta-lactamase from Bacillus cereus 569/H. It cross-links SER 70 and LYS 234 as it binds in a similar to 1:1 rati o. The cross-linked enzyme is irreversibly inhibited while the seconda ry structure is partially stabilized under conditions when the native enzyme is otherwise converted to a form with no detectable secondary s tructure by circular dichroism. (C) 1995 Academic Press, Inc.