Structural highlights
5w7a is a 2 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| Gene: | AOAH (European rabbit) |
| Activity: | Acyloxyacyl hydrolase, with EC number 3.1.1.77 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[AOAH_RABIT] Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses. In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria.[UniProtKB:O35298]
Publication Abstract from PubMed
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.
Crystal structure of the mammalian lipopolysaccharide detoxifier.,Gorelik A, Illes K, Nagar B Proc Natl Acad Sci U S A. 2018 Jan 17. pii: 1719834115. doi:, 10.1073/pnas.1719834115. PMID:29343645[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gorelik A, Illes K, Nagar B. Crystal structure of the mammalian lipopolysaccharide detoxifier. Proc Natl Acad Sci U S A. 2018 Jan 17. pii: 1719834115. doi:, 10.1073/pnas.1719834115. PMID:29343645 doi:http://dx.doi.org/10.1073/pnas.1719834115
