E. coli lipid

Single crystals of free lipid A or LPS are as yet not available. Therefore, the most promising approach to obtain molecular models is to perform theoretical calculations. After the chemical structures of enterobacterial lipid A had been elucidated, this methodology was successfully applied with heptaacyl S. minnesota lipid A (220) and hexaacyl E. coli Re LPS (221). As an example, Fig. 13 shows the atomic model of the E. coli lipid A molecule, as calculated by Kastowsky et al. (221) using energy-minimization techniques. 

Fig. 13.—Ball-and-stick (A) and space-filling (B) atomic models of E. coli lipid A. One out of several possible conformers is shown. The ring plane (right) of GlcN(II) almost coincides with the plane of the paper (221). Courtesy of Dr. Manfred Kastowsky, University of Berlin.

The results from all biological assays performed showed that chemically synthesized E. coli lipid A (compound 506 or LA-15-PP) expresses, with similar doses, the same spectrum of endotoxic effects as bacterial (E. coli) free lipid A (5,234-237). Thus, lipid A constitutes the lethal, pyrogenic, leukopenic, and mediator-inducing, that is, the endotoxically essential region of LPS, its endotoxic properties being embedded in a molecule having the structure shown in Fig. 2. 

Fig. 1.3 Various structures of lipid A in different bacteria. The most conserved part of lipid A is its backbone, disaccharide of glucosamine. The groups connecting to the backbone of lipid A could be different from one bacterium to another. (A) In E. coli lipid A there are two phosphates and six fatty acid chains connecting to the backbone. (B) In F. tularensis lipid A there are only one phosphate and four fatty acid chains. (C) In the lipid A of S. typhimurium there is an additional second fatty acid chain at 2-position. (D) In R. etli lipid A there is a very long fatty acid chain at...

A FIGURE 7-11 Structural model of E coli lipid flippase, an ABC protein homologous to mammalian MDRl. The... 

When a solution of E. coli lipid vesicles was incrementally supplemented with a concentrated octylglucoside (OG) solution, exothermic heat pulses were observed, indicative of the integration of the detergent into the vesicular phase. The subsequent steep descent in heat output reported... 

Figure 3. Other regulated acylation reactions involved in E. coli lipid A biosynthesis under special conditions. The reactions catalyzed by LpxP (formerly known as Ddg) [59] and LpxY (also known as PagP or CrcA) [51] are shown. LpxP is a cold induced protein which incorporates an unsaturated 16 carbon fatty acyl chain in place of the laurate normally incorporated by HtrB. LpxY, the expression of which is activated by the PhoP/PhoQ system [51], is an outer membrane protein that incorporates palmitate to make hepta-acylated lipid A. LpxY is capable of acylating lipid X, lipid IVa, and lipid A, as well as Kdo2-lipid IVa (as shown). The physiological substrate is probably lipid A, given that LpxY is an outer membrane protein.

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