Inhibition of ligand exchange kinetics via active-site trapping with an antibody fragment.

TitleInhibition of ligand exchange kinetics via active-site trapping with an antibody fragment.
Publication TypeJournal Article
Year of Publication2014
AuthorsOyen, D., Steyaert J., and Barlow J. N.
JournalBiochemistry
Volume53
Issue12
Pagination1879-81
Date Published2014 Apr 01
ISSN1520-4995
KeywordsCatalytic Domain, Crystallography, X-Ray, Escherichia coli, Kinetics, Ligands, Protein Structure, Secondary, Single-Domain Antibodies, Tetrahydrofolate Dehydrogenase
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.

DOI10.1021/bi500110j
Alternate JournalBiochemistry
PubMed ID24617671
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