PM0188 is a newly identified sialyltransferase from P. multocida which transfers sialic acid from cytidine 5′-monophosphonuraminic acid (CMP-NeuAc) to an acceptor sugar. Although sialyltransferases are involved in important biological functions like cell-cell recognition, cell differentiation and receptor-ligand interactions, little is known about their catalytic mechanism. Here, we report the X-ray crystal structures of PM0188 in the presence of an acceptor sugar and a donor sugar analogue, revealing the precise mechanism of sialic acid transfer. Site-directed mutagenesis, kinetic assays, and structural analysis show that Asp141, His311, Glu338, Ser355 and Ser356 are important catalytic residues; Asp141 is especially crucial as it acts as a general base. These complex structures provide insights into the mechanism of sialyltransferases and the structure-based design of specific inhibitors.
|Number of pages||7|
|Journal||Journal of Biochemistry and Molecular Biology|
|Publication status||Published - 2008 Jan 1|
All Science Journal Classification (ASJC) codes
- Molecular Biology