Biosynthesis and structure-activity relationships of the lipid a family of glycolipids.

Biosynthesis and structure-activity relationships of the lipid a family of glycolipids. Curr Opin Chem Biol. 2017 Sep 19;40:127-137 Authors: Xiao X, Sankaranarayanan K, Khosla C Abstract Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the amphipathic glycolipid moiety of LPS. It stimulates the immune system by tightly binding to Toll-like receptor 4. More recently, Lipid A has also been shown to activate intracellular caspase-4 and caspase-5. An impressive diversity is observed in Lipid A structures from different Gram-negative bacteria, and it is well established that subtle changes in chemical structure can result in dramatically different immune activities. For example, Lipid A from Escherichia coli is highly toxic to humans, whereas a biosynthetic precursor called Lipid IVA blocks this toxic activity, and monophosphoryl Lipid A from Salmonella minnesota is a vaccine adjuvant. Thus, an understanding of structure-activity relationships in this glycolipid family could be used to design useful immunomodulatory agents. Here we review the biosynthesis, modification, and structure-activity relationships of Lipid A. PMID: 28942130 [PubMed - as supplied by publisher]
Source: Current Opinion in Chemical Biology - Category: Biochemistry Authors: Tags: Curr Opin Chem Biol Source Type: research