6DK5

The X-ray crystal structure of human endothelin-1, a polypeptide hormone regulator of blood pressure

6DK5 の概要

• エントリーDOI: 10.2210/pdb6dk5/pdb
• 分子名称: Endothelin-1 (2 entities in total)
• 機能のキーワード: blood pressure, vasoconstrictor, sarafotoxins, polypeptide, hypertension, diabetes, stroke, hormone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4995.90

構造登録者

McPherson, A. (登録日: 2018-05-28, 公開日: 2019-01-02, 最終更新日: 2024-11-20)

主引用文献

McPherson, A.,Larson, S.B.
The X-ray crystal structure of human endothelin 1, a polypeptide hormone regulator of blood pressure.
Acta Crystallogr F Struct Biol Commun, 75:47-53, 2019

PubMed Abstract: Human endothelin is a 21-amino-acid polypeptide, constrained by two intra-chain disulfide bridges, that is made by endothelial cells. It is the most potent vasoconstrictor in the body and is crucially important in the regulation of blood pressure. It plays a major role in a host of medical conditions, including hypertension, diabetes, stroke and cancer. Endothelin was crystallized 28 years ago in the putative space group P622, but the structure was never successfully solved by X-ray diffraction. Using X-ray diffraction data from 1992, the structure has now been solved. Assuming a unit cell belonging to space group P6 and a twin fraction of 0.28, a solution emerged with two, almost identical, closely associated molecules in the asymmetric unit. Although the data extended to beyond 1.8 Å resolution, a model containing 25 waters was refined to 1.85 Å resolution with an R of 0.216 and an R of 0.284. The disulfide-constrained `core' of the molecule, amino-acid residues 1-15, has a main-chain conformation that is essentially the same as endothelin when bound to its receptor, but many side-chain rotamers are different. The carboxy-terminal `tail' comprising amino-acid residues 16-21 is extended as when receptor-bound, but it exhibits a different conformation with respect to the `core'. The dimer that comprises the asymmetric unit is maintained almost exclusively by hydrophobic interactions and may be stable in an aqueous medium.

PubMed: 30605125
DOI: 10.1107/S2053230X18016011

実験手法

X-RAY DIFFRACTION (1.85 Å)