UDP-N-acetylglucosamine--undecaprenyl-phosphate sugar-1-phosphate transferase (WecA) (WecA)

UDP-N-acetylglucosamine--undecaprenyl-phosphate sugar-1-phosphate transferase (WecA) is an essential integral membrane enzyme in Gram-negative bacteria that initiates the synthesis of several vital cell surface polysaccharides (UniProt P06103). It catalyzes the transfer of N-acetylglucosamine-1-phosphate from UDP-GlcNAc to the lipid carrier undecaprenyl phosphate, forming the first lipid-linked intermediate for O-antigen and enterobacterial common antigen (ECA) pathways (Valvano, 2011, PMID: 21421926). These surface structures are critical for maintaining the integrity of the bacterial cell envelope and protecting the pathogen from host immune defenses and environmental stressors. As WecA is conserved across many pathogenic species and is located on the cytoplasmic face of the inner membrane, it represents a significant target for novel antibiotic development (Lehrer et al., 2007, PMID: 17606600). However, the development of therapeutic inhibitors is complicated by the structural similarity between WecA and the human enzyme DPAGT1, which is involved in essential N-linked protein glycosylation (Price et al., 2016, PMID: 27551059). Consequently, achieving high selectivity for the bacterial enzyme over the human counterpart is a primary challenge in drug discovery efforts targeting WecA.

Other names

GlcNAc-1-P transferaseUDP-GlcNAc:undecaprenyl-phosphate GlcNAc-1-phosphate transferaserfe gene productTagO (Gram-positive homolog)

Inhibition of the transfer of N-acetylglucosamine-1-phosphate from UDP-GlcNAc to undecaprenyl phosphate, thereby blocking the initiation of O-antigen and ECA biosynthesis (Valvano, 2011, PMID: 21421926).