A structural insight into the molecular recognition of a (-)-Delta9-tetrahydrocannabinol and the development of a sensitive, one-step, homogeneous immunocomplex-based assay for its detection

Journal of Molecular Biology
Merja H NiemiKristiina Takkinen

Abstract

(-)-Delta9-tetrahydrocannabinol (THC) is the main psychoactive compound found in cannabis. In this study, an anti-THC Fab fragment, designed T3, was isolated from a display library cloned from the spleen cells of a mouse immunized with a THC-bovine serum albumin conjugate, and the crystal structures of the T3 Fab in its free form and in complex with THC were determined at 1.9 A and 2.0 A resolution, respectively. The THC binding site of the T3 Fab is a narrow cavity: the n-pentyl group of THC protrudes deep into the interface area between the variable domains and the C(10) monoterpene moiety of the hapten is partially exposed to solvent. The metabolites of THC, with modifications in the C(10) monoterpene moiety, 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol and 11-hydroxy-?(9)-tetrahydrocannabinol, are bound by the T3 Fab with a higher affinity than THC. The crystal structures suggest that Ser52H and Arg53H of the T3 Fab are able to make hydrogen bonds with the metabolites, which leads to an increased binding against these metabolites. By developing a T3 Fab-Delta(9)-THC immunocomplex binding antibody from a naïve antibody phage display library, the specificity of the Delta(9)-THC binding is highly increased, which allows a on...Continue Reading

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Aug 20, 1987·Journal of Molecular Biology·C Chothia, A M Lesk
Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E F UllmanC Skold
Feb 10, 2000·Acta Crystallographica. Section D, Biological Crystallography·J ValjakkaJ Rouvinen
Aug 22, 2001·Protein Science : a Publication of the Protein Society·A E KisterI M Gelfand
Aug 25, 2001·Journal of Chromatography. a·T K NevanenT T Teeri
May 31, 2002·Pharmacological Reviews·A C HowlettR G Pertwee
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Mar 1, 2003·Science·Leo C JamesDan S Tawfik
Sep 10, 2003·Yeast·Mirka ReinmanKristiina Takkinen
Nov 20, 2003·Nature Structural Biology·Hoa P NguyenStephen V Evans
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Apr 15, 2005·Analytical Chemistry·Timo PulliKristiina Takkinen
Oct 11, 2005·Biochemical and Biophysical Research Communications·Saoirse E O'SullivanMichael D Randall
Feb 25, 2006·Journal of Molecular Biology·Robyn L StanfieldBernhard Rupp
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Dec 3, 2013·Database : the Journal of Biological Databases and Curation·Jasmine Y YoungHelen M Berman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.