Structure of the presynaptic (Y2) receptor-specific neuropeptide Y analog ANA-NPY.
Neuropeptide Y analog ANA-NPY or [Leu-17, Gln-19, Ala-20, Ala-23, Leu-28, Leu-31]NPY(13-36)-amide binds to postjunctional or Y1 receptors to raise blood pressure and to prejunctional or Y2 receptors to inhibit neurotransmitter release. ANA-NPY affects Y2 receptors in the same way as intact NPY but exhibits far less potent effects on Y1 receptors. The structure of ANA-NPY was examined using two-dimensional proton nuclear magnetic resonance spectroscopy. Complete assignment of all backbone and side chain hydrogens was accomplished with totally correlated spectroscopy (TOCSY) experiments providing through-bond 1H-1H connectivities, and nuclear Overhauser effect spectroscopy (NOESY), providing the through-space and sequential backbone connectivities. The tertiary solution structure of the peptide was performed using distance geometry and dynamic simulated annealing. ANA-NPY exhibits a helical structure with strong amphipathic character with a bend around Glu-24 indicating that the C-terminal segment 25-35 forms a single alpha-helical motif.
Barden
J A
JA
Department of Anatomy and Histology, University of Sydney, NSW, Australia.
Cuthbertson
R M
RM
Potter
E K
EK
D000595:Amino Acid Sequence; D001665:Binding Sites; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D017661:Receptors, Presynaptic / Q000737:chemistry*; D013329:Structure-Activity Relationship
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017661:Receptors, Presynaptic; C094733:neuropeptide Y(13-36)amide, N-acetyl-(Leu(17,28,31)Gln(19)Ala(20,23))-