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Open data
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Basic information
Entry | Database: PDB / ID: 7rkz | ||||||
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Title | Structure of ACLY D1026A-substrates-asym-int | ||||||
![]() | ATP-citrate synthase | ||||||
![]() | TRANSFERASE / mutant | ||||||
Function / homology | ![]() ATP citrate synthase activity / ATP citrate synthase / Fatty acyl-CoA biosynthesis / citrate metabolic process / ChREBP activates metabolic gene expression / acetyl-CoA biosynthetic process / oxaloacetate metabolic process / coenzyme A metabolic process / lipid biosynthetic process / cholesterol biosynthetic process ...ATP citrate synthase activity / ATP citrate synthase / Fatty acyl-CoA biosynthesis / citrate metabolic process / ChREBP activates metabolic gene expression / acetyl-CoA biosynthetic process / oxaloacetate metabolic process / coenzyme A metabolic process / lipid biosynthetic process / cholesterol biosynthetic process / tricarboxylic acid cycle / fatty acid biosynthetic process / azurophil granule lumen / ficolin-1-rich granule lumen / Neutrophil degranulation / extracellular exosome / extracellular region / nucleoplasm / ATP binding / membrane / metal ion binding / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||
![]() | Wei, X. / Marmorstein, R. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Allosteric role of the citrate synthase homology domain of ATP citrate lyase. Authors: Xuepeng Wei / Kollin Schultz / Hannah L Pepper / Emily Megill / Austin Vogt / Nathaniel W Snyder / Ronen Marmorstein / ![]() ![]() Abstract: ATP citrate lyase (ACLY) is the predominant nucleocytosolic source of acetyl-CoA and is aberrantly regulated in many diseases making it an attractive therapeutic target. Structural studies of ACLY ...ATP citrate lyase (ACLY) is the predominant nucleocytosolic source of acetyl-CoA and is aberrantly regulated in many diseases making it an attractive therapeutic target. Structural studies of ACLY reveal a central homotetrameric core citrate synthase homology (CSH) module flanked by acyl-CoA synthetase homology (ASH) domains, with ATP and citrate binding the ASH domain and CoA binding the ASH-CSH interface to produce acetyl-CoA and oxaloacetate products. The specific catalytic role of the CSH module and an essential D1026A residue contained within it has been a matter of debate. Here, we report biochemical and structural analysis of an ACLY-D1026A mutant demonstrating that this mutant traps a (3S)-citryl-CoA intermediate in the ASH domain in a configuration that is incompatible with the formation of acetyl-CoA, is able to convert acetyl-CoA and OAA to (3S)-citryl-CoA in the ASH domain, and can load CoA and unload acetyl-CoA in the CSH module. Together, this data support an allosteric role for the CSH module in ACLY catalysis. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 714.4 KB | Display | ![]() |
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PDB format | ![]() | 585.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 113.7 KB | Display | |
Data in CIF | ![]() | 170.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 24511MC ![]() 7rigC ![]() 7rmpC ![]() 8g1eC ![]() 8g1fC ![]() 8g5cC ![]() 8g5dC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 120940.125 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 6 types, 178 molecules ![](data/chem/img/ADP.gif)
![](data/chem/img/Q5B.gif)
![](data/chem/img/FLC.gif)
![](data/chem/img/COA.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/Q5B.gif)
![](data/chem/img/FLC.gif)
![](data/chem/img/COA.gif)
![](data/chem/img/HOH.gif)
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-FLC / #5: Chemical | Mass: 767.534 Da / Num. of mol.: 2 / Source method: obtained synthetically #6: Chemical | ChemComp-COA / #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: ACLY D1026A mutant in complex with CoA and citrate / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.48 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 4.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 237362 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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