2SOC

NMR STUDY OF THE BACKBONE CONFORMATIONAL EQUILIBRIA OF SANDOSTATIN, TWO REPRESENTATIVE MINIMUM ENERGY PARTIALLY HELICAL STRUCTURES

2SOC の概要

• エントリーDOI: 10.2210/pdb2soc/pdb
• 分子名称: SANDOSTATIN (1 entity in total)
• 機能のキーワード: octreotide, sandostatin
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1022.26

構造登録者

Melacini, G.,Zhu, Q.,Goodman, M. (登録日: 1996-11-26, 公開日: 1997-04-21, 最終更新日: 2023-11-15)

主引用文献

Melacini, G.,Zhu, Q.,Goodman, M.
Multiconformational NMR analysis of sandostatin (octreotide): equilibrium between beta-sheet and partially helical structures.
Biochemistry, 36:1233-1241, 1997

PubMed Abstract: This paper reports a detailed conformational analysis by 1H NMR (DMSO-d6, 300 K) and molecular modeling of the octapeptide D-Phe1-Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7+ ++-Thr8-ol (disulfide bridged) known as sandostatin (or SMS 201-995 or octreotide) with both somatostatin-like and opioid-like bioactivities. This is the initial report on sandostatin showing that attempts to explain all NMR data using a single average conformation reveal several important inconsistencies including severe violations of mutually exclusive backbone-to-backbone NOEs. The inconsistencies are solved by assuming an equilibrium between antiparallel beta-sheet structures and conformations in which the C-terminal residues form a 3(10) helix-like fold (helical ensemble). This conformational equilibrium is consistent with previous X-ray diffraction investigations which show that sandostatin can adopt both the beta-sheet and the 3(10) helix-like secondary structure folds. In addition, indications of a conformational equilibrium between beta-sheet and helical structures are also found in solvent systems different from DMSO-d6 and for other highly bioactive analogs of sandostatin. In these cases a proper multiconformational NMR refinement is important in order to avoid conformational averaging artifacts. Finally, using the known models for somatostatin-like and opioid-like bioactivities of sandostatin analogs, the present investigation shows the potentials of the proposed structures for the design of novel sandostatin-based conformationally restricted peptidomimetics. These analogs are expected to refine the pharmacophore models for sandostatin bioactivities.

PubMed: 9063871
DOI: 10.1021/bi962497o

実験手法

SOLUTION NMR