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From Proteopedia

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 . For succinyl CoA synthetase, we observe that alpha helices are the major contributor to the protein structure, with the observed by the white lines connecting the carbon backbone. For the beta sheets, we can use the backbone to distinguish the antiparallel and parallel sheets. The antiparallel sheets are denoted by parallel white lines connecting the sheets whereas nonparallel white lines indicate the presence of two adjacent parallel sheets.

Another important factor in protein analysis is knowing where the hydrophobic and hydrophilic residues are. While the and the in ribbon form are visually appealing, it is usually more useful to approach these residues with a stick/wireframe representation. 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.

Another important factor to consider the solvent accessibility of solvent molecules. 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 observe 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 interactions (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 exercise caution here in noting what we consider to be the ligands. Sulfate and phosphate are typically solvents located in the crystal structure of the protein, so they are not the true ligands that we are interested in. On the other hand, we are interested in CoA and glycerol as they are the true ligands that are bound to the enzyme to facilitate the catalysis. Noting this caveat, we can also observe the with the ligands. The color of the ligands are coded as such: CoA (fuchsia), phosphate (green), sulfate (purple) and glycerol (indigo). As mentioned earlier, 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 while 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.

Succinyl CoA synthetase's 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). This active sites are responsible for catalyzing the succinate formation from succinyl-CoA.