5GSF

Structure of roseltide rT1

Summary for 5GSF

• Entry DOI: 10.2210/pdb5gsf/pdb
• NMR Information: BMRB: 36016
• Descriptor: roseltide rT1 (1 entity in total)
• Functional Keywords: cysteine rich peptide, neutrophil elastase inhibitor, roseltide, hydrolase inhibitor
• Biological source: Hibiscus sabdariffa
• Total number of polymer chains: 1
• Total formula weight: 2629.22

Authors

Xiao, T.,Tam, J.P. (deposition date: 2016-08-16, release date: 2017-01-25, Last modification date: 2024-10-16)

Primary citation

Loo, S.,Kam, A.,Xiao, T.,Nguyen, G.K.,Liu, C.F.,Tam, J.P.
Identification and Characterization of Roseltide, a Knottin-type Neutrophil Elastase Inhibitor Derived from Hibiscus sabdariffa.
Sci Rep, 6:39401-39401, 2016

PubMed Abstract: Plant knottins are of therapeutic interest due to their high metabolic stability and inhibitory activity against proteinases involved in human diseases. The only knottin-type proteinase inhibitor against porcine pancreatic elastase was first identified from the squash family in 1989. Here, we report the identification and characterization of a knottin-type human neutrophil elastase inhibitor from Hibiscus sabdariffa of the Malvaceae family. Combining proteomic and transcriptomic methods, we identified a panel of novel cysteine-rich peptides, roseltides (rT1-rT8), which range from 27 to 39 residues with six conserved cysteine residues. The 27-residue roseltide rT1 contains a cysteine spacing and amino acid sequence that is different from the squash knottin-type elastase inhibitor. NMR analysis demonstrated that roseltide rT1 adopts a cystine-knot fold. Transcriptome analyses suggested that roseltides are bioprocessed by asparagine endopeptidases from a three-domain precursor. The cystine-knot structure of roseltide rT1 confers its high resistance against degradation by endopeptidases, 0.2 N HCl, and human serum. Roseltide rT1 was shown to inhibit human neutrophil elastase using enzymatic and pull-down assays. Additionally, roseltide rT1 ameliorates neutrophil elastase-stimulated cAMP accumulation in vitro. Taken together, our findings demonstrate that roseltide rT1 is a novel knottin-type neutrophil elastase inhibitor with therapeutic potential for neutrophil elastase associated diseases.

PubMed: 27991569
DOI: 10.1038/srep39401

Experimental method

SOLUTION NMR