title: Inhibition of ligand exchange kinetics via active-site trapping with an antibody fragment.
abstract: We describe the first example of an inhibitory antibody fragment (nanobody ca1697) that binds simultaneously to an enzyme (the enzyme dihydrofolate reductase from Escherichia coli) and its bound substrate (folate). Binding of the antibody to the substrate causes a 20-fold reduction in the rate of folate exchange kinetics. This work opens up the prospect of designing new types of antibody-based inhibitors of enzymes and receptors through suitable design of immunogens.
authors.affiliation: Structural Biology Brussels, Vrije Universiteit Brussel , Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Oyen
authors.forename: Jan
authors.initials: J
authors.lastname: Steyaert
authors.forename: John N
authors.initials: JN
authors.lastname: Barlow
mesh_terms: D020134:Catalytic Domain / Q000502:physiology; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008024:Ligands; D017433:Protein Structure, Secondary; D061905:Single-Domain Antibodies / Q000737:chemistry* / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D061905:Single-Domain Antibodies; D013762:Tetrahydrofolate Dehydrogenase