1UYB

THE SOLUTION STRUCTURE OF THE B-FORM OF UROGUANYLIN-16 NMR, 10 STRUCTURES

1UYB の概要

• エントリーDOI: 10.2210/pdb1uyb/pdb
• 分子名称: UROGUANYLIN-16, ISOMER B (1 entity in total)
• 機能のキーワード: hormone, guanylyl cyclase c activation, isomer a, peptide hormone, solution structure, topological stereoisomer, uroguanylin
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q16661
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1671.89

構造登録者

Marx, U.C.,Adermann, K.,Forssmann, W.-G.,Roesch, P. (登録日: 1997-09-11, 公開日: 1998-03-18, 最終更新日: 2024-10-23)

主引用文献

Marx, U.C.,Klodt, J.,Meyer, M.,Gerlach, H.,Rosch, P.,Forssmann, W.G.,Adermann, K.
One peptide, two topologies: structure and interconversion dynamics of human uroguanylin isomers.
J.Pept.Res., 52:229-240, 1998

PubMed Abstract: The peptide hormone uroguanylin stimulates chloride secretion via activation of intestinal guanylyl cyclase C (GC-C). It is characterized by two disulfide bonds in a 1-3/2-4 pattern that causes the existence of two topological stereoisomers of which only one induces intracellular cGMP elevation. To obtain an unambiguous structure-function relationship of the isomers, we determined the solution structure of the separated uroguanylin isoforms using NMR spectroscopy. Both isomers adopt well-defined structures that correspond to those of the isomers of the related peptide guanylin. Furthermore, the structure of the GC-C-activating uroguanylin isomer A closely resembles the structure of the agonistic Escherichia coli heat-stable enterotoxin. Compared with guanylin isomers, the conformational interconversion of uroguanylin isomers is retarded significantly. As judged from chromatography and NMR spectroscopy, both uroguanylin isoforms are stable at low temperatures, but are subject to a slow pH-dependent mutual isomerization at 37 degrees C with an equilibrium isomer ratio of approximately 1:1. The conformational exchange is most likely under the sterical control of the carboxy-terminal leucine. These results imply that GC-C is activated by ligands exhibiting the molecular framework corresponding to the structure of uroguanylin isomer A.

PubMed: 9774236

実験手法

SOLUTION NMR