Refinement of the solution structure of the heparin-binding domain of vascular endothelial growth factor using residual dipolar couplings.
Previous NMR structural studies of the heparin-binding domain of vascular endothelial growth factor (VEGF165) revealed a novel fold comprising two subdomains, each containing two disulfide bridges and a short two-stranded antiparallel beta-sheet. The mutual orientation of the two subdomains was poorly defined by the NMR data. Heteronuclear relaxation data suggested that this disorder resulted from a relative lack of experimental restraints due to the limited size of the interface, rather than inherent high-frequency flexibility. Refinement of the structure using 1H(N-15N residual dipolar coupling restraints results in significantly improved definition of the relative subdomain orientations.
Stauffer
Melissa E
ME
Department of Protein Engineering, Genentech, Inc., South, San Francisco, CA 94080, USA.
Skelton
Nicholas J
NJ
Fairbrothe
Wayne J
WJ
D001665:Binding Sites; D016228:Endothelial Growth Factors / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D008222:Lymphokines / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006493:Heparin