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

Journal of Molecular Biology
C FrancartG Lippens

Abstract

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 beta-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 beta-sheet and a single fourth disulfide bridge links the binding loop to the central beta-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, alre...Continue Reading

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Citations

Apr 17, 2010·American Journal of Respiratory Cell and Molecular Biology·Jean-Michel Sallenave
Apr 8, 2010·Biological Chemistry·Nicolas GuyotNoel G McElvaney
Dec 2, 2008·Internal Medicine·Toshiki MizunoMasanori Nakagawa
Oct 12, 2004·Fish & Shellfish Immunology·Jyh-Yih ChenChing-Ming Kuo
Jan 29, 2008·Developmental and Comparative Immunology·Valerie J SmithChris Hauton
Jan 1, 2008·Molecular Reproduction and Development·Navneet SharmaDerrick Rancourt
Feb 28, 2018·Nature Structural & Molecular Biology·Colin E CorrentiRoland K Strong
Feb 22, 2002·European Journal of Biochemistry·Zoltán GáspáriAndrás Perczel
Apr 12, 2001·European Journal of Biochemistry·J C MartinsS J Wodak
Mar 12, 2008·The FEBS Journal·Maelíosa T C McCruddenDavid J Timson
Dec 9, 2016·Biological Chemistry·Donna M SmallClifford C Taggart
Dec 13, 2005·Clinical Science·Steven E WilliamsJean-Michel Sallenave
Feb 19, 2000·Journal of Molecular Graphics & Modelling·S RanganathanK R Nicholas
Oct 11, 2005·Journal of Proteome Research·Marc S CorteseA Keith Dunker

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