Solution structure of R-elafin, a specific inhibitor of elastase

The solution structure of r-elafin, a specific elastase inhibitor, has been determined using NMR spectroscopy. Characterized by a flat core and a flexible N-terminal extremity, the three-dimensional structure is formed by a central twisted β-hairpin accompanied by two external segments linked by the...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 1997-05, Vol.268 (3), p.666-677
Main Authors: Francart, Céline, Dauchez, Manuel, Alix, Alain J.P., Lippens, Guy
Format: Article
Language:English
Subjects:
Amino Acid Sequence
binding loop
Crystallography, X-Ray
disulfide bridges
elastase inhibitor
Enzyme Inhibitors
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Sequence Data
NMR
Pancreatic Elastase - antagonists & inhibitors
Proline - chemistry
Protein Conformation
Protein Structure, Secondary
Proteinase Inhibitory Proteins, Secretory
Proteins - chemistry
SLPI
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The solution structure of r-elafin, a specific elastase inhibitor, has been determined using NMR spectroscopy. Characterized by a flat core and a flexible N-terminal extremity, the three-dimensional structure is formed by a central twisted β-hairpin accompanied by two external segments linked by the proteinase binding loop. A cluster of three disulfide bridges connects the external segments to the central β-sheet and a single fourth disulfide bridge links the binding loop to the central β-turn. The same spatial distribution of disulfide bridges can be observed in both domains of the secretory leukocyte protease inhibitor (SLPI), another elastase inhibitor. The structural homology between r-elafin and the C-terminal domain of SLPI confirms the former as a second member of the chelonianin family of proteinase inhibitors. Based on the homology between the two proteins and recent results obtained for elastase binding mutants of the bovine pancreatic trypsin inhibitor (BPTI), we define the segment 22 to 27 as the binding loop of elafin, with the scissile peptide bond between Ala24 and Met25. In our solution structures, this loop is extended and solvent-exposed, and exhibits a large degree of flexibility. This mobility, already observed for the binding loop in other protease inhibitors in solution, might be an important feature for the interaction with the corresponding protease.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.1997.0983