Conformation of the second disulfide loop in human transforming growth factor‐α studied by two‐dimensional nmr spectroscopy

Abstract

AbstractThe determination of the conformation of a cyclic heptadecapeptide derived from the second loop of human transforming growth factor‐α, [Ala21]‐hTGF‐α‐(16–32), is described. Two‐dimensional homonuclear Hartmann–Hahn and rotating‐frame cross‐relaxation spectroscopy in H2O were used to obtain the complete proton resonance assignments and the necessary distance constraints between nonbonded hydrogen atoms to derive a conformation without involving any energy minimization. The result is an ellipsoidal‐shaped structure with a turn at Gly19 and a bend formed by residues 26–29, Gln‐Glu‐Asp‐Lys. Comparison is made with the second loop of human epidermal growth factor and the results are discussed in terms of receptor binding and biological activity.