Title : Crystal structure of the mammalian lipopolysaccharide detoxifier
Abstract :
- LPS is a potent bacterial endotoxin that triggers the innate immune system
- Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion
- Acyloxyacyl hydrolase ( AOAH ) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS , rendering it immunologically inert
- This activity is critical for recovery from immune tolerance that follows Gram-negative infection
- To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS
- The substrate's lipid moiety is accommodated in a large hydrophobic pocket formed by the saposin and catalytic domains with a secondary acyl chain inserted into a narrow lateral hydrophobic tunnel at the active site
- The enzyme establishes dispensable contacts with the phosphate groups of LPS but does not interact with its oligosaccharide portion
- Proteolytic processing allows movement of an amphipathic helix possibly involved in substrate access at membranes
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*Output_Site_Fusion* (sent_index,
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