Determination of protein-ligand binding modes using complexation-induced changes in (1)h NMR chemical shift. 2008

Marina Cioffi, and Christopher A Hunter, and Martin J Packer, and Andrea Spitaleri
Department of Chemistry, Centre for Chemical Biology, Krebs Institute for Biomolecular Science, University of Sheffield, Sheffield S3 7HF, U.K.

A new method for determining three-dimensional solution structures of protein-ligand complexes using experimentally determined complexation-induced changes in (1)H NMR chemical shift (CIS) is introduced. The method has been validated using the complex formed between the protein antitumor antibiotic neocarzinostatin (NCS) and a synthetic chromophore analogue. The X-ray crystal structure of the unbound protein and the backbone amide proton CIS were the input data used in the determination of the three-dimensional structure of the complex. The experimental CIS values were used in a continuous direct structure refinement process based on genetic algorithms to sample conformational space. The calculated structure of the complex agrees well with the NMR solution structure, indicating the potential of this approach for structure determination.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D019906 Nuclear Magnetic Resonance, Biomolecular NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope. Biomolecular Nuclear Magnetic Resonance,Heteronuclear Nuclear Magnetic Resonance,NMR Spectroscopy, Protein,NMR, Biomolecular,NMR, Heteronuclear,NMR, Multinuclear,Nuclear Magnetic Resonance, Heteronuclear,Protein NMR Spectroscopy,Biomolecular NMR,Heteronuclear NMR,Multinuclear NMR,NMR Spectroscopies, Protein,Protein NMR Spectroscopies,Spectroscopies, Protein NMR,Spectroscopy, Protein NMR

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