5W78

Human acyloxyacyl hydrolase (AOAH), proteolytically processed

Summary for 5W78

• Entry DOI: 10.2210/pdb5w78/pdb
• Descriptor: Acyloxyacyl hydrolase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, MYRISTIC ACID, ... (8 entities in total)
• Functional Keywords: lipopolysaccharide, lps, gdsl esterase, saposin, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 66284.66

Authors

Gorelik, A.,Illes, K.,Nagar, B. (deposition date: 2017-06-19, release date: 2018-01-03, Last modification date: 2024-10-30)

Primary citation

Gorelik, A.,Illes, K.,Nagar, B.
Crystal structure of the mammalian lipopolysaccharide detoxifier.
Proc. Natl. Acad. Sci. U.S.A., 115:E896-E905, 2018

PubMed 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.

PubMed: 29343645
DOI: 10.1073/pnas.1719834115

Experimental method

X-RAY DIFFRACTION (2.271 Å)