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From Proteopedia

Revision as of 04:07, 17 October 2013

is a key enzyme in the citric acid cycle of cellular metabolism. Its main role is to catalyze the formation of succinate from succinyl-CoA. First, the succinyl-CoA complex undergoes nucleophilic attack by a phosphate molecule, releasing CoA in the process. This phospho-succinate complex then reacts with a histidine group on the enzyme to release succinate (the key compound required for the next step of the citric acid cycle). The phospho group on the histidine subsequently reacts with ADP to form ATP. This specific crystal structure of succinyl CoA synthetase was synthesized by Frazer et al. (Acta Cryst. (2007). D63, 876–884) and given the PDB code 2NU8. The form isolated is doubly dimeric protein with the known binding ligands present in the protein crystallization. The four chains depicted: , , and , where chains A and D, B and E are dimers.

As much as we like the ribbon model of proteins, we also need to visualize succinyl CoA synthetase in its . This model gives us a better picture of the Van der Waal radii and packing of the side chains, details usually not obtained by the use of the ribbon model. However, with the ribbon model, it is often easier to visualize the present in the enzyme's secondary structure. Here we observe the presence of and . In the beta sheet structure, we observe

Here's some for the beta sheet.

Here are the

We can see the here while the are visible as well.

We can get a clearer picture of the chains as stick and wire models in the presence of the rest of the molecule. The maroon chains represent the hydrophobic residues seen earlier while the transparent part of the protein shows the other residues present. We can invert this image to obtain the , which are shown in light brown. We can see that the hydrophobic residues are mostly located on the interior of the protein while the hydrophilic residues are mostly interacting with the protein's exterior.

Water is often crystallized with the protein, and we can show portions of where water molecules (light blue) interacts with the chain. We can also analyze the presence of ligand molecules at sites, where CoA (fuchsia), phosphate (green) and glycerol (indigo) bind.

We can also see the same effects for the other chains: 's water interactions (in red) are depicted and its sites are also observed (CoA (fuchsia), sulfate (purple)). 's water (in red) are depicted. Its binding sites are also observed (CoA (fuchsia), glycerol (indigo). 's water interactions (in red) are depicted and its binding sites are also observed (CoA (fuchsia), sulfate (purple).

We can also see the with the ligands. The color of the ligands are coded as such: CoA (fuchsia), phosphate (green), sulfate (purple) and glycerol (indigo). The sulfate and phosphate molecules are not particularly important as they are more of solvent molecules rather than ligands. The major species here are the CoA and glycerol molecules. The glycerol molecule is surrounded by hydrophobic residues (depicted by the white-colored side chains) whereas the CoA molecule has hydrophilic residues (Lys) stabilizing the negatively charged phosphate groups while hydrophobic residues (e.g. Ile, Pro,) stabilize the rest of the CoA. For chains A and D, the glycerol binds to sites I221, V225, T226, K227, P228, V229, A228, G269 and V270 CoA binds to these sites G14, T16, G17, S18, Q19, V38, T39, P40, K42, Y71, V72, P73, F76, S80, I95, T96, E97, N122, T123, P124, I136 For chains B and E, CoA binds to these sites R29, E33, S36, K66, G265, A266, G267, G320, G321, V323, R324, C325, I328, L349, E350, G351, N352

Its are on chains A and B. On , the glutamic acid residue at position 208 and the histidine residue at position 246 while for (shown in pink), its catalytic residues are the tyrosine residue at position 109 and the glutamic acid residue at position 197 (shown in blue).