The crystal structure of mouse IRG1 suggests that cis-aconitate decarboxylase has an open and closed conformation

Itaconate, produced as an offshoot of the TCA cycle, is a multifunctional immunometabolite possessing antibacterial, antiviral, immune regulation, and tumor progression activities. The production of itaconate in biological systems is catalyzed by cis-aconitate decarboxylase (CAD, also known as immune responsive gene 1 (IRG1) in mammals). In this study, we solved the structure of IRG1 from Mus musculus (mouse IRG1). Structural comparison analysis revealed that IRG1 can exist in either an open or closed conformation and that this is controlled by the A1 loop located proximal to the active site. Our closed form structure was maintained by an unidentified molecule in the active site, which might mimic its substrate. Protein Data Bank accession codes Coordinate and structural factors were deposited with the Protein Data Bank under PDB ID: 7BR9.

1 Overall quality at a glance i ○ The following experimental techniques were used to determine the structure: X-RAY DIFFRACTION The reported resolution of this entry is 3.29 Å.
Percentile scores (ranging between 0-100) for global validation metrics of the entry are shown in the following graphic.The table shows the number of entries on which the scores are based.The table below summarises the geometric issues observed across the polymeric chains and their fit to the electron density.The red, orange, yellow and green segments on the lower bar indicate the fraction of residues that contain outliers for >=3, 2, 1 and 0 types of geometric quality criteria respectively.A grey segment represents the fraction of residues that are not modelled.

Metric
The numeric value for each fraction is indicated below the corresponding segment, with a dot representing fractions <=5% The upper red bar (where present) indicates the fraction of residues that have poor fit to the electron density.The numeric value is given above the bar.
Mol Chain Length Quality of chain 2 Entry composition i ○ There are 2 unique types of molecules in this entry.The entry contains 6986 atoms, of which 0 are hydrogens and 0 are deuteriums.
In the tables below, the ZeroOcc column contains the number of atoms modelled with zero occupancy, the AltConf column contains the number of residues with at least one atom in alternate conformation and the Trace column contains the number of residues modelled with at most 2 atoms.
5 Model quality i ○

Standard geometry i ○
The Z score for a bond length (or angle) is the number of standard deviations the observed value is removed from the expected value.A bond length (or angle) with |Z| > 5 is considered an outlier worth inspection.RMSZ is the root-mean-square of all Z scores of the bond lengths (or angles).There are no bond angle outliers.

Mol
There are no chirality outliers.
There are no planarity outliers.

Too-close contacts i ○
In the following The all-atom clashscore is defined as the number of clashes found per 1000 atoms (including hydrogen atoms).The all-atom clashscore for this structure is 3.

RNA i ○
There are no RNA molecules in this entry.

Non-standard residues in protein, DNA, RNA chains i ○
There are no non-standard protein/DNA/RNA residues in this entry.

Carbohydrates i ○
There are no monosaccharides in this entry.

Ligand geometry i ○
There are no ligands in this entry.

Other polymers i ○
There are no such residues in this entry.

Polymer linkage issues i ○
The following chains have linkage breaks:

Ligands i ○
There are no ligands in this entry.

Other polymers i ○
There are no such residues in this entry.
property plots i ○ These plots are drawn for all protein, RNA, DNA and oligosaccharide chains in the entry.The first graphic for a chain summarises the proportions of the various outlier classes displayed in the second graphic.The second graphic shows the sequence view annotated by issues in geometry and electron density.Residues are color-coded according to the number of geometric quality criteria for which they contain at least one outlier: green = 0, yellow = 1, orange = 2 and red = 3 or more.A red dot above a residue indicates a poor fit to the electron density (RSRZ > 2).Stretches of 2 or more consecutive residues without any outlier are shown as a green connector.Residues present in the sample, but not in the model, are shown in grey.
Data and refinement statistics i ○ Xtriage's analysis on translational NCS is as follows: The largest off-origin peak in the Patterson function is 4.78% of the height of the origin peak.No significant pseudotranslation is detected.
table, the Non-H and H(model) columns list the number of non-hydrogen atoms and hydrogen atoms in the chain respectively.The H(added) column lists the number of hydrogen atoms added and optimized by MolProbity.The Clashes column lists the number of clashes within the asymmetric unit, whereas Symm-Clashes lists symmetry related clashes.