Conformational selection in trypsin-like proteases.
For over four decades, two competing mechanisms of ligand recognition--conformational selection and induced-fit--have dominated our interpretation of protein allostery. Defining the mechanism broadens our understanding of the system and impacts our ability to design effective drugs and new therapeutics. Recent kinetics studies demonstrate that trypsin-like proteases exist in equilibrium between two forms: one fully accessible to substrate (E) and the other with the active site occluded (E*). Analysis of the structural database confirms existence of the E* and E forms and vouches for the allosteric nature of the trypsin fold. Allostery in terms of conformational selection establishes an important paradigm in the protease field and enables protein engineers to expand the repertoire of proteases as therapeutics.
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, United States.
Nicola
N
Pozzi
Austin D
AD
Vogt
David W
DW
Gohara
Enrico
E
Di Cera
D000465:Algorithms; D000494:Allosteric Regulation; D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D015202:Protein Engineering; D012697:Serine Endopeptidases / Q000737:chemistry*
D012697:Serine Endopeptidases