Ligand-Induced Strain in Hydrogen Bonds of the c-Src SH3 Domain Detected by NMR

摘要: Changes in the molecular conformation of proteins can result from a variety perturbations, and play crucial roles regulation biological activity. A new solution NMR method has been applied to monitor ligand-induced changes hydrogen bond geometry chicken c-Src SH3 domain. The structural response this domain ligand binding investigated by measuring trans-hydrogen (15)N-(13)C' scalar couplings free state when bound high affinity class I RLP2, containing residues RALPPLPRY. comparison between bonds resolution X-ray structures those observed via (h3)J(NC') shows remarkable agreement. Two backbone-to-side-chain are solution, each appears role stabilization loop structure. Reproducible across that translate into length ranging 0.02 0.12 A. be rationalized an induced fit mechanism which protein participate compensatory forces imparted at protein-ligand interface. Upon binding, mutual intercalation two Leu-Pro segments three aromatic side-chains protruding surface wedges apart secondary elements within This disruption is transmitted domino-like effect through networks bonded peptide planes. unprecedented obtained demonstrates ability characterize subtle rearrangements upon perturbation, represents step endeavor understand how contribute function macromolecules.