1D1E
SOLUTION STRUCTURE OF LACTAM-BRIDGED C-TERMINAL ANALOGUE-II OF NEUROPEPTIDE Y
Summary for 1D1E
| Entry DOI | 10.2210/pdb1d1e/pdb |
| Related | 1D0W |
| NMR Information | BMRB: 5215 |
| Descriptor | C-TERMINAL ANALOGUE OF NEUROPEPTIDE Y, A POTENT Y2 RECEPTOR AGONIST (1 entity in total) |
| Functional Keywords | lactam-bridge, helix, neuropeptide |
| Total number of polymer chains | 1 |
| Total formula weight | 1704.98 |
| Authors | Yao, S.,Norton, R.S. (deposition date: 1999-09-15, release date: 2000-06-17, Last modification date: 2024-10-16) |
| Primary citation | Yao, S.,Smith-White, M.A.,Potter, E.K.,Norton, R.S. Stabilization of the helical structure of Y2-selective analogues of neuropeptide Y by lactam bridges. J.Med.Chem., 45:2310-2318, 2002 Cited by PubMed 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. PubMed: 12014969DOI: 10.1021/jm010543z PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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