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Department of Chemistry
Durham University, Durham, UK
Crystal Structure of Protein Kinase A/PKI (5-24)
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| Structural Features | Catalytic Site |
Shaltiel, S., Cox, S. and Taylor,
S. S., Proc. Natl. Acad. Sci. USA, 1998, 95, 484-491.
Hemmer, W., McGlone, M., Tsigelny, I. and Taylor, S. S., J. Biol. Chem.,
1997, 272, 16946-16954.
Protein Kinase A (PKA) is a cytosolic protein that catalyses the O-phosphorylation of protein and peptide substrates. The structure above is the catalytic subunit, with the peptide inhibitor PKI (5-24) bound in the active site. The phosphate group is transferred to the substrate from ATP, which is bound to the catlalytic subunit with Mn(II) in a pocket formed by a glycine-rich loop and thus shielded from the bulk solvent. The glycine-rich loop also contributes to catalysis. The backbone amides of Phe54 and Gly55 bind the β-phosphate group of ATP, and the backbone amide of Ser53 forms a hydrogen bond with the γ-phosphate. The side chains of Ser53 and Thr51 are involved in hydrogen bonding interactions with PKI (5-24). The active site of the enzyme contains several ordered water molecules that perform various roles - some are associated with metal binding sites, some with the active site and some with ligand binding. The catalytic subunit is a flexible molecule, displaying 'open' and 'closed' confomations and marked flexibility within the glycine-rich loop. Asp166 and Lys168 perform the roles of base and transition state stabilisation respectively.