PDBsum entry 1d1e

Neuropeptide

PDB id: 1d1e

Contents

Protein chain

14 a.a.

PDB id:

1d1e

Name:

Neuropeptide

Title:

Solution structure of lactam-bridged c-terminal analogue-ii of neuropeptide y

Structure:

C-terminal analogue of neuropeptide y, a potent y2 receptor agonist. Chain: a. Fragment: c-terminal analogue. Engineered: yes. Mutation: yes. Other_details: synthetic with mutation i28k, t32e and a lactam-bridge was introduced between positions (28) and (32)

Source:

Synthetic: yes. Other_details: chemically synthesized.

NMR struc:

20 models

Authors:

S.Yao,R.S.Norton

Key ref:

S.Yao et al. (2002). Stabilization of the helical structure of Y2-selective analogues of neuropeptide Y by lactam bridges. J Med Chem, 45, 2310-2318. PubMed id: 12014969 DOI: 10.1021/jm010543z

Date:

15-Sep-99 Release date: 17-Jun-00

Protein chain

No UniProt id for this chain

Struc: 13 a.a.

DOI no: 10.1021/jm010543z

J Med Chem 45:2310-2318 (2002)

PubMed id: 12014969

Stabilization of the helical structure of Y2-selective analogues of neuropeptide Y by lactam bridges.

S.Yao, M.A.Smith-White, E.K.Potter, R.S.Norton.

ABSTRACT

The importance of helical structure in an analogue of NPY selective for the Y2 receptor, Ac[Leu28,31]NPY24-36, has been investigated by introducing a lactam bridge between positions 28 and 32. The resulting analogue, Ac-cyclo28/32[Ala24,Lys28,Leu31,Glu32]NPY24-36, is a potent Y2-selective agonist. Structural analysis by NMR shows that this analogue forms a helical structure in a 40% trifluoroethanol/water mixture, whereas in water only the region around the lactam bridge (Lys28-Glu32) adopts helical-like structure, with both N- and C-termini being poorly defined. The observation of well-defined helical structure in aqueous TFE contrasts with that reported for a similar analogue, Ac-cyclo28/32[Lys28,Glu32]NPY25-36 (Rist et al. FEBS Lett. 1996, 394, 169-173), which consisted of a hairpin-like structure that brought the N- and C-termini into proximity. We have therefore determined the structures of this analogue, as well as those of Ac-cyclo28/32[Ala24,Lys28,Leu31,Glu32]NPY24-36 and Ac-cyclo28/32[Ala24,Lys28,Glu32]NPY24-36, under identical solution conditions (30% TFE/H2O mixture at 308 K) and find essentially the same helical structure in all three peptides. These findings support the proposal that these Y2-selective analogues adopt a helical structure when bound to the Y2 receptor.