Among the seven lytic transglycosilases of Escherichia coli, only MltE appears to be primarily endolytic in its cleavage of the �-1,4-glycosidic bond between the MurNAc and GlcNAc sugars of the cell-wall peptidoglycan. The reaction is thought to occur in four steps that involve higher-energy sugar conformations, leading to the formation of a 1,6-anhydro-N-acetyl-muramyl moiety in the peptidoglycan. With the recently constructed computational model of the peptidoglycan bound to MltE in hand, we have carried out hybrid quantum mechanical/molecular mechanical (QM/MM) studies to elucidate reaction energetics. We utilized the ONIOM method implemented in Gaussian 09 with the density functional theory methods to calculate potential energy surfaces of each reaction step. A fully ab initio model system in the absence of the enzyme was studied first, followed by the QM/MM calculations of the full enzymatic system. The energy landscapes provided important insights of how the MurNAc conformational changes are brought about within the enzyme and their energetics. We observed that certain transformations that appear to be readily feasible in the model system would either prefer a slightly different path or would not happen at all within the enzyme environment.

Hybrid QM/MM studies of the reaction energetics of lytic transglycosilase E (MltE) of <i>Escherichia coli</i>

246th National Meeting (2013)

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Hybrid QM/MM studies of the reaction energetics of lytic transglycosilase E (MltE) of Escherichia coli