7rbx | pdb_00007rbx

Crystal structure of isocitrate lyase and phosphorylmutase:isocitrate lyase from Brucella melitensis biovar Abortus 2308 bound to itaconic acid

spinqualitylabelsall models 7rbx, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rbx is a 4 chain structure with sequence from Brucella abortus 2308. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: EDO, ITN, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2YQA0_BRUA2 Publication Abstract from PubMed Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with Brucella in C57BL/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using RNA sequencing, we identified the aconitate decarboxylase 1 gene (Acod1; also known as Immune responsive gene 1), as one of the genes most upregulated in murine AMs in response to B. melitensis infection at 24 hours post-infection. Upregulation of Acod1 was confirmed by RT-qPCR in lungs infected with B. melitensis and B. abortus. We observed that Acod1-/- C57BL/6 mice display a higher bacterial load in their lungs than wild-type (wt) mice following B. melitensis or B. abortus infection, demonstrating that Acod1 participates in the control of pulmonary Brucella infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. Dimethyl itaconate (DMI), a chemically-modified membrane permeable form of itaconate, has a dose-dependent inhibitory effect on Brucella growth in vitro. Interestingly, structural analysis suggests the binding of itaconate into the binding site of B. abortus isocitrate lyase. DMI does not inhibit multiplication of the isocitrate lyase deletion mutant DeltaaceA B. abortus in vitro. Finally, we observed that, unlike the wt strain, the DeltaaceA B. abortus strain multiplies similarly in wt and Acod1-/- C57BL/6 mice. These data suggest that bacterial isocitrate lyase might be a target of itaconate in AMs. Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice.,Demars A, Vitali A, Comein A, Carlier E, Azouz A, Goriely S, Smout J, Flamand V, Van Gysel M, Wouters J, Abendroth J, Edwards TE, Machelart A, Hoffmann E, Brodin P, De Bolle X, Muraille E PLoS Pathog. 2021 Sep 15;17(9):e1009887. doi: 10.1371/journal.ppat.1009887., eCollection 2021 Sep. PMID:34525130 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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