biostudies-literatureMorea VNHLBI NIH HHSAndrea BellelliNIH HHSEnrico Di Cera and Progetto POR FESR LazioNational Institutes of Health Research1651https://www.ebi.ac.uk/biostudies/studies/S-EPMC9687781biostudies-literatureUnknown12(11)Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the "concerted model" by Monod, Wyman, and Changeux in 1965. Since its inception, this model of cooperativity was seen as distinct from and not reducible to the "sequential model" originally formulated by Pauling in 1935, which was developed further by Koshland, Nemethy, and Filmer in 1966. However, it is difficult to decide which model is more appropriate from equilibrium or kinetics measurements alone. In this paper, we examine several cooperative proteins whose functional behavior, whether sequential or concerted, is established, and offer a combined approach based on BiomoleculesStructural Basis of Sequential and Concerted Cooperativity.PMC9687781R01 HL049413R01 HL147821HL139554R01 HL139554HL147821HL049413PROT. N. A0375-2020-36575HL049413, HL139554 and HL147821Angelucci FBellelli ADi Cera ETame JRHMorea VfalseStructural Basis of Sequential and Concerted Cooperativity.Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the "concerted model" by Monod, Wyman, and Changeux in 1965. Since its inception, this model of cooperativity was seen as distinct from and not reducible to the "sequential model" originally formulated by Pauling in 1935, which was developed further by Koshland, Nemethy, and Filmer in 1966. However, it is difficult to decide which model is more appropriate from equilibrium or kinetics measurements alone. In this paper, we examine several cooperative proteins whose functional behavior, whether sequential or concerted, is established, and offer a combined approach based on 2022-01-01T00:00:00Z2022 Nov2025-04-18T20:33:41.414Z2025-04-07T08:30:00.839ZS-EPMC96877813635900010.3390/biom12111651