The structural basis of allosteric regulation in proteins

Abstract 

Allosteric regulation of protein function occurs when the regulatory trigger, such as the binding of a small-molecule effector or inhibitor, takes place some distance from the protein’s, or protein complex’s, active site. This distance can be a few Å, or tens of Å. Many proteins are regulated in this way and exhibit a variety of allosteric mechanisms. Here we review how analyses of experimentally determined models of protein 3D structures, using either X-ray crystallography or NMR spectroscopy, have revealed some of the mechanisms involved.

Abbreviations: BoNT/A, botulinum neurotoxin type A, CAK, CDK-activating kinase, CDK, cyclin-dependent kinase, DAHP, 3-deoxy-d-arbino-heptulosonate-7-phosphate, DAHPS, DAHP synthase, DBD, DNA-binding domain, DHDPS, dihydrodipicolinate synthase, DHFR, dihydrofolate reductase, E4P, d-erythrose-4-phosphate, FlAsH, fluorescin arsenical hairpin binder, hPTP1E, human tyrosine phosphatase 1E, KNF, Koshland, Nemethy and Filmer model, MWC, Monod, Wyman and Changeux model, NBD, nucleotide binding domain, PDB, Protein Data Bank, PEP, phosphoenolpyruvate, PGDH, phosphoglycerate dehydrogenase, PTS, phosphotransferase system, RBD, regulatory binding domain, SBD, substrate binding domain

Keywords: Allosteric regulation, Protein structure, Ligand binding, Phosphorylation