Substrate-bound crystal structures reveal features unique to Mycobacterium tuberculosis N-acetyl-glucosamine 1-phosphate uridyltransferase and a catalytic mechanism for acetyl transfer.

ABSTRACT: N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmU), a bifunctional enzyme involved in bacterial cell wall synthesis is exclusive to prokaryotes. GlmU, now recognized as a promising target to develop new antibacterial drugs, catalyzes two key reactions: acetyl transfer and uridyl transfer at two independent domains. Hitherto, we identified GlmU from Mycobacterium tuberculosis (GlmU(Mtb)) to be unique in possessing a 30-residue extension at the C terminus. Here, we present the crystal structures of GlmU(Mtb) in complex with substrates/products bound at the acetyltransferase active site. Analysis of these and mutational data, allow us to infer a catalytic mechanism operative in GlmU(Mtb). In this S(N)2 reaction, His-374 and Asn-397 act as catalytic residues by enhancing the nucleophili

SUBMITTER: Jagtap PK 

PROVIDER: S-EPMC3501063 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature