Focus on the active site for the complete reaction cycle of human phosphoglycerate kinase. By combining high resolution X-ray crystallography and solution small angle scattering the complete reaction cycle has been determined. The enzyme starts the cycle fully open and ready to bind ligands, as the domains move together ADP (top) and 1,3 bisphosphoglycerate (13BPG - bottom) are bound moving essential sidechains into place for catalysis. As the enzyme closes fully the ligands are brought together and a phosphate group transferred from 13BPG to ADP to form ATP. Once catalysis has occurred the hydrophobic patch destabilizes the closed conformation, opening the protein and leading to the release of products. The protein is then ready to start the cycle again.
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