There are two chemically reasonable mechanisms that could generate the observed product of lysozymeb mediated cleavage of the glycosidic bond. Phillips and colleagues proposed a dissociative (SN1-type) mechanism (Fig. 6–28a, left), in which the GlcNAc initially dissociates in step to leave behind a glycosyl cation (a carbocation) intermediate. In this mechanism, the departing GlcNAc is protonated by general acid catalysis by Glu35, located in a hydrophobic pocket that gives its carboxyl group an unusually high pKa. The carbocation is stabilized by resonance involving the adjacent ring oxygen, as well as by electrostatic interaction with the negative charge on the nearby Asp52. In step water attacks at C-1 of Mur2Ac to yield the product. The alternative mechanism (Fig. 6–28a, right) involves two consecutive direct displacement (SN2-type) steps. In step 1, Asp52 attacks C-1 of Mur2Ac to displace the GlcNAc. As in the first mechanism, Glu35 acts as a general acid to protonate the departing GlcNAc. In step 2, water attacks at C-1 of Mur2Ac to displace the Asp52 and gen-erate product.
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