PDBsum entry 5w7c

Hydrolase

PDB id: 5w7c

Contents

Protein chains

111 a.a.

420 a.a.

Ligands

NAG-NAG ×4

NAG ×4

FTT ×4

DAO-FTT ×2

Metals

_CA ×6

Waters ×295

PDB id:

5w7c

Name:

Hydrolase

Title:

Human acyloxyacyl hydrolase (aoah), proteolytically processed, s263a mutant, with lps

Structure:

Acyloxyacyl hydrolase. Chain: a, b. Fragment: n-terminal residues 24-152. Engineered: yes. Acyloxyacyl hydrolase. Chain: c, d. Fragment: c-terminal residues 153-575. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: aoah. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_taxid: 7108

Resolution:

2.23Å R-factor: 0.213 R-free: 0.245

Authors:

A.Gorelik,K.Illes,B.Nagar

Key ref:

A.Gorelik et al. (2018). Crystal structure of the mammalian lipopolysaccharide detoxifier. Proc Natl Acad Sci U S A, 115, E896. PubMed id: 29343645

Date:

19-Jun-17 Release date: 03-Jan-18

Protein chains

P28039  (AOAH_HUMAN) -  Acyloxyacyl hydrolase from Homo sapiens

Seq: 575 a.a.

Struc: 111 a.a.

Protein chains

P28039  (AOAH_HUMAN) -  Acyloxyacyl hydrolase from Homo sapiens

Seq: 575 a.a.

Struc: 420 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, C, B, D: E.C.3.1.1.77 - acyloxyacyl hydrolase.
• Pathway: EC 3.1.1.77
• Reaction: a 3-(acyloxy)acyl derivative of bacterial toxin + H2O = a 3-hydroxyacyl derivative of bacterial toxin + a fatty acid + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

Proc Natl Acad Sci U S A 115:E896 (2018)

PubMed id: 29343645

Crystal structure of the mammalian lipopolysaccharide detoxifier.

A.Gorelik, K.Illes, B.Nagar.

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.