Background: Multidrug resistant Gram negative pathogens pose a persistent threat to the
health care system and require investigation of new targets and molecules for the development of antibiotics
to treat infections caused by MDR bacterial pathogens.
Objective: It is essential to work on multidisciplinary approaches and diverse strategies for developing
new compounds acting on novel antibacterial targets. N-acetylglucosamine-1-phosphateuridyltransferase/
glucosamine-1-phosphate-acetyltransferase (GlmU) is one such target which is involved
in the synthesis of both peptidoglycan and Lipopolysaccharide in Gram negative and Gram
positive bacteria making GlmU an attractive target for developing antibacterials.
Results: GlmU, as revealed by X- ray crystallographic studies, is made up of two domains connected
by α helical arm; the N-terminal uridyltransferase domain resembles a dinucleotide Rossmann fold and
the C- terminal acetyltransferase domain adopts a left handed parallel β helix structure. The GlmU
molecules are arranged in a trimeric array, the acetyltransferase active site being formed at the junction
of adjacent LβH domain. Many potent inhibitors of both the acetyltransferase and uridyltransferase
activity of GlmU have been identified. Inhibitors of the acetyltransferase activity of GlmU include
nonspecific thiol reactive agents, 2-phenylbenzofurans, arylamines and arylsulfonamides. A
aminopiperidine based inhibitor has also been reported to inhibit uridyltransferase activity of hiGlmU.
Conclusion: The present review provides an insight of the structure of GlmU and its reported inhibitors
which make GlmU a potential target for drug designing. The GlmU is a promising target for drug
discovery against Gram negative pathogens and future studies should focus on GlmU for the development
of more potent compounds for treating Gram negative infections.