The class D �-lactamases are characterized by the presence of a carboxylated lysine in the active site that participates in catalysis. OXA-24 is a class D enzyme exhibiting resistance to most available �-lactamase inhibitors. Here details of its reaction with a 6-alkylidiene penam sulfone inhibitor, SA-1-204, provide novel insight into the enzyme's mode of action. The reaction between SA-1-204 in single crystals of OXA-24 is followed by Raman microscopy. When the crystal holding solution contains 28% PEG 2000, the reaction is seen to undergo only one cycle and  the OXA-24 is no longer active. This is attributed to the decarboxylation of Lys-84 during the first reaction cycle. Using absorbance spectroscopy, activity could be restored by reacting aqueous OXA-24 with a large excess of NaHCO3.

Carboxylation and decarboxylation of active site lysine 84 controls the activity of OXA-24 β-lactamase: Raman crystallographic and solution evidence

244th National Meeting (2012)

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