Deletion of a single amino acid changes the folding of an apamin hybrid sequence peptide to that of endothelin. Biopolymers 1997 Apr 05;41(4):451-60
Date
04/05/1997Pubmed ID
9080780DOI
10.1002/(SICI)1097-0282(19970405)41:4<451::AID-BIP9>3.0.CO;2-LScopus ID
2-s2.0-0031553985 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
The solution conformations of a hybrid sequence peptide related to the bee venom peptide apamin have been determined using two-dimensional 1H-nmr. Apamin is an 18 amino acid peptide containing a C-terminal helix that is stabilized by two disulfide bonds. The deletion of one residue (K4) of the N-terminal "scaffold" region of the apamin sequence results in a helical peptide, but with a change in the pairing of cysteines to form the disulfide cross links. The new disulfide arrangement is analogous to that of the vasoconstrictor peptide endothelin. Two sets of nmr resonances were observed for the apamin-deletion (AD) peptide, due to cistrans isomerism at the A4-P5 peptide bond. The cis isomer of the AD peptide contains a tight turn in residues 3-6, which is required for formation of the alpha-helix in residues 7-15. Nuclear Overhauser effects observed for the trans AD peptide are not consistent with any single unique fold, indicating the presence of conformational averaging when the peptide adopts the trans form. Distance geometry calculations on the cis AD peptide reveal an alpha-helical structure that appears to be more like that of apamin than the crystal structure of human endothelin, despite the reversal of the disulfide pattern in the AD peptide from that of apamin to that of endothelin.
Author List
Volkman BF, Wemmer DEAuthor
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApamin
Endothelin-1
Humans
Magnetic Resonance Spectroscopy
Models, Molecular
Protein Conformation
Protein Folding
Sequence Deletion
