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 β-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. [ABSTRACT FROM AUTHOR]