Citrate Synthase

3D Structure of Citrate Synthase

CPK Color Scheme C O N P S

Citrate Synthase is an enzyme that catalyzes the first step in the citric acid cycle. Oxaloacetate and acetyl-CoA bind to Citrate Synthase, which then catalyzes the reaction which joins the two compounds together.

Learning the Structure of Citrate Synthase:

To return the protein to the original view, click

here.

In eukaryotes, Citrate Synthase is a dimer, meaning that it is a protein which is composed of two separate amino acid chains which are not covalently bonded to each other. Click

here to see the two subunits that compose the dimer. Each subunit is colored differently - one is blue, and the other is green.

The conformation for Citrate Synthase changes when oxaloacetate (OAA) binds to citrate synthase. This conformational change creates the acetyl-CoA binding site. Once OAA is bound, the binding constant for acetyl-CoA is increased by a factor of 20. To see OAA, click

here. (OAA will appear as red spacefill molecules, while the two subunits appear as blue and green.) As you can see, there are two binding sites for OAA.

The site where oxaloacetate is bound (the active site) is largely polar. To see a close-up of this site with the polar atoms colored cyan, oxaloacteate colored red, and non-polar atoms colored yellow, click

here. To see the polars in spacefill with OAA in wireframe, click

here. Notice that when you rotate the enzyme, the OAA molecule appears closer to polar residues than non-polar residues.

Citrate Synthase consists almost entirely of helices. To view the helices of Citrate Synthase, click

here. To view the helices and the hydrogen bonds which hold the helices together, click

here.

The amino acids that are located near the oxaloacetate are involved in the catalyzation of the reaction, serving mostly as acids and bases. To see the residues involved in the catalyzation, click

here. HIS 320 is colored purple, HIS 274 is colored green, and Asp 375 is colored blue. The two histidine residues act as acids, and the asp residue acts as a base during the reaction.

3D Structure of Citrate Synthase and Reaction Products

After OAA is bound to the enzyme, acetyl-CoA binds. The enzyme then catalyses the following reactions: enolization of the acetyl-CoA by removing the methyl group, a Claisen condensation which joins the enolated acetyl-CoA and the oxaloacetate creating citryl-CoA, then a thioester hydrolysis which creates citrate and CoA.

The monomer of Citrate Synthase, pictured in the lower frame of the left side of this screen shows the citrate synthase enzyme bound to the two products - citrate (click

here) and CoA (click

here). To see both citrate and CoA, click

here.

To see an image of the reactions that citrate synthase catalyses, click Here.

3D Structure of *Citrate Synthase*

3D Structure of Citrate Synthase and Reaction Products

3D Structure of Citrate Synthase