Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzymes, VanT and similar proteins
This subfamily is composed of Enterococcus gallinarum VanT and similar proteins. VanT is a membrane-bound serine racemase (EC 5.1.1.18) that is essential for vancomycin resistance in Enterococcus gallinarum. It converts L-serine into its D-enantiomer (D-serine) for peptidoglycan synthesis. The C-terminal region of this protein contains a PLP-binding TIM-barrel domain followed by beta-sandwich domain, which is homologous to the fold type III PLP-dependent enzyme, bacterial alanine racemase (AR). AR exists as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. On the basis of this similarity, it has been suggested that dimer formation of VanT is required for its catalytic activity, and that it catalyzes the racemization of serine in a mechanistically similar manner to that of alanine by bacterial AR. Some biochemical evidence indicates that VanT also exhibits alanine racemase activity and plays a role in the racemization of L-alanine. VanT contains a unique N-terminal transmembrane domain, which may function as an L-serine transporter. VanT serine racemases are not related to eukaryotic serine racemases, which are fold type II PLP-dependent enzymes.
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