1uyb
From Proteopedia
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THE SOLUTION STRUCTURE OF THE B-FORM OF UROGUANYLIN-16 NMR, 10 STRUCTURES
Overview
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.
About this Structure
1UYB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
One peptide, two topologies: structure and interconversion dynamics of human uroguanylin isomers., Marx UC, Klodt J, Meyer M, Gerlach H, Rosch P, Forssmann WG, Adermann K, J Pept Res. 1998 Sep;52(3):229-40. PMID:9774236
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