title: Identification of Hydrophobic Interfaces in Protein-Ligand Complexes by Selective Saturation Transfer NMR Spectroscopy.
abstract: The proper characterization of protein-ligand interfaces is essential for structural biology, with implications ranging from the fundamental understanding of biological processes to pharmacology. Nuclear magnetic resonance is a powerful technique for such studies. We propose a novel approach to the direct determination of the likely pose of a peptide ligand onto a protein partner, by using frequency-selective cross-saturation with a low stringency isotopic labeling methods. Our method illustrates a complex of the Src homology 3 domain of C-terminal Src kinase with a peptide from the proline-enriched tyrosine phosphatase.
authors.affiliation: New York Structural Biology Center, New York, NY 10027, USA. fabien.ferrage@ens.fr.|Department of Chemistry, École Normale Supérieure-PSL Research University, 24 rue Lhomond, 75005 Paris, France. fabien.ferrage@ens.fr.|LBM, Sorbonne Universités, UPMC Univ Paris 06, 4 place Jussieu, F-75005 Paris, France. fabien.ferrage@ens.fr.|UMR 7203 LBM, CNRS, F-75005 Paris, France. fabien.ferrage@ens.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Ferrage
authors.affiliation: New York Structural Biology Center, New York, NY 10027, USA. kskdutta@gmail.com.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Dutta
authors.affiliation: New York Structural Biology Center, New York, NY 10027, USA. david.cowburn@einstein.yu.edu.|Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA. david.cowburn@einstein.yu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Cowburn
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D000081247:CSK Tyrosine-Protein Kinase; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry*
chemical_list: D008024:Ligands; D010446:Peptide Fragments; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases
keywords: NMR; SH3 ligand; cross-saturation; interface identification