title: Conformational and receptor binding properties of human EGF and TGF-alpha second loop fragments.
abstract: The solution conformation of the second loop fragment of human EGF, [Ala20] EGF (14-31), was determined using two-dimensional NMR homonuclear Hartmann-Hahn and rotating frame nuclear Overhauser enhancement spectroscopy. The results are compared with the conformation of the second loop fragment of human TGF-alpha, [Ala21] TGF-alpha(16-32), and with that of the second loop of intact EGF. Comparison of the two experimentally determined structures of the second loop fragments shows significant differences in the turn regions of each peptide. For the EGF fragment, hydrophobic side chain groups protrude away from the ring, whereas for the TGF-alpha fragment hydrophilic groups are directed away from the ring. Although these turn regions represent the putative receptor binding sites, neither second loop fragment binds to the EGF receptor. The biological activity is discussed in terms of the conformational differences found for the two second loop fragments.
authors.affiliation: Laboratory of Chemistry, NHLBI, National Institutes of Health, Bethesda, MD 20892.
authors.forename: K H
authors.initials: KH
authors.lastname: Han
authors.forename: J A
authors.initials: JA
authors.lastname: Ferretti
authors.forename: C H
authors.initials: CH
authors.lastname: Niu
authors.forename: V
authors.initials: V
authors.lastname: Lokeshwar
authors.forename: R
authors.initials: R
authors.lastname: Clarke
authors.forename: D
authors.initials: D
authors.lastname: Katz
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism; D011487:Protein Conformation; D015291:Transforming Growth Factors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors