Where is citrate synthase

In the second tetramer right , one of the CoA-binding domains was not modelled owing to disorder. The CCS modules are shown in surface mode. Distinct structural regions are coloured according to the colouring scheme in Fig.

Strictly conserved residues are white against a black background. Conserved residues at the ACLY two-helix pivot are indicated with a purple arrow.

Bound CoA is shown as coloured spheres. Top secondary structure elements correspond to H. The active site residues of CS are indicated by a purple arrow. CoA is shown by sticks.

Active-site residues are highlighted according to the numbering scheme in chicken CS. His, highlighted in yellow, is not conserved in ACLY sequences. For clarity, only the helical secondary structure elements are shown. Dashed lines indicate polar interactions. Starting from a final dataset of 27, particles, initial models were made using the stochastic gradient descent method in RELION2.

Subsequent 3D classification was performed using the C1, C2 or D2 starting models as an input, again applying C1, C2 or D2 symmetry, respectively. Although 3D classification using D2 symmetry results in two classes displaying all four CCS modules class 1 and 4 , subsequent 3D refinement in C2 using an averaged map of these two classes resulted in a disappearance of two CCS modules in the lower half of hACLY, pointing to flexibility of the peripheral domains of hACLY.

Supplementary Figure 1 - Uncropped scans with size marker indications. The latter model was generated by merging a model of the human CCL module with all four protomers in the closed state, with four CCS modules reoriented to match the CCS modules in the C.

Reprints and Permissions. Verschueren, K. Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle. Nature , — Download citation. Received : 18 October Accepted : 08 March Published : 03 April Issue Date : 25 April Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Journal of NeuroVirology By submitting a comment you agree to abide by our Terms and Community Guidelines.

If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Advanced search. Skip to main content Thank you for visiting nature. Subjects Cancer metabolism Enzyme mechanisms Fat metabolism Molecular evolution X-ray crystallography.

Access through your institution. Buy or subscribe. Rent or Buy article Get time limited or full article access on ReadCube.

References 1. PubMed Google Scholar 6. CAS Google Scholar PubMed Google Scholar Google Scholar Acknowledgements K. Reviewer information Nature thanks Frank M. Verschueren View author publications. View author publications. Ethics declarations Competing interests The authors declare no competing interests. Extended data figures and tables. Extended Data Fig. Extended Data Table 1 Crystallographic data and refinement statistics Full size table.

Supplementary information Supplementary Figure Supplementary Figure 1 - Uncropped scans with size marker indications. Reporting Summary. Video 2: Shuttling of the citryl-CoA intermediate between the citryl-CoA synthetase and lyase modules. CarbonylDB database of protein carbonylation sites More CarbonylDB i. PhosphoSitePlus i. SwissPalm database of S-palmitoylation events More SwissPalm i. Bgee i.

ExpressionAtlas i. Genevisible search portal to normalized and curated expression data from Genevestigator More Genevisible i. Human Protein Atlas More HPA i. BioGRID i. CORUM i. Protein interaction database and analysis system More IntAct i. RNAct i. SMR i. Database of comparative protein structure models More ModBase i. PDBe-KB i.

Ensembl GeneTree More GeneTree i. InParanoid i. OMA i. Database of Orthologous Groups More OrthoDB i. Database for complete collections of gene phylogenies More PhylomeDB i. TreeFam database of animal gene trees More TreeFam i. Gene3D i. Integrated resource of protein families, domains and functional sites More InterPro i. Pfam protein domain database More Pfam i.

Protein Motif fingerprint database; a protein domain database More Superfamily database of structural and functional annotation More Citrate synthase Citrate synthase. Citrate synthase, mitochondrial Citrate synthase, mitochondrial. Perhaps the most crucial regulators of the citrate synthase reaction are its substrates, acetyl-CoA and oxaloacetate. Both are present in the mitochondria at concentrations below saturation of citrate synthase.

The metabolic flux is controlled by substrate availability, so controlling the levels of acetyl-CoA and oxaloacetate in the mitochondria controls the rate of reaction. Furthermore, citrate synthase is inhibited by NADH, which competes with oxaloacetate , and succinyl-CoA an example of competitive feedback inhibition [8].

In many plants, bacteria and fungi, such as the peroxisomes of baker's yeast, citrate synthase plays a role in the glyoxylate cycle [9] [10] [11]. Citrate Synthase 3D structures.

The lower image is colored to highlight the similarity with the eukaryotic enzyme. The citrate synthase enzyme found in many bacteria is larger than ours, as seen in this structure of the enzyme from Escherichia coli PDB entry 1nxg. It is composed of six identical subunits, but if you look from the side as shown in the lower picture , you can see that each pair of subunits has a similar Z shape as our enzyme.

The bacterial enzyme has an additional site that binds to NADH, shown here in magenta. Binding of NADH slows the action of the enzyme. This helps the cell regulate its level of energy production: high levels of NADH mean that the cell has plenty of energy, so it doesn't need to break down any more sugar. Citrate synthase is found in all living cells, so it has been a useful enzyme for comparing differences from organism to organism.

In particular, it has been used to study the unusual adaptations in cells that live in extreme environments. Structures have been obtained from organisms that live in very cold environments see, for instance, PDB entry 1a59 , not shown here and others that live in hot environments. The enzyme shown here, from PDB entry 2ibp, has an interesting structural feature that allows it to resist high temperatures. Each chain has a disulfide linkage that closes the chain into a loop.