RBI, a one-domain alpha-amylase/trypsin inhibitor with completely independent binding sites

FEBS Letters
K MaskosR Glockshuber

Abstract

The bifunctional inhibitor from Ragi (Eleusine coracana Gaertneri) (RBI) is the only member of the alpha-amylase/trypsin inhibitor family that inhibits both trypsin and alpha-amylase. Here, we show that both enzymes simultaneously and independently bind to RBI. The recently solved three-dimensional NMR structure of RBI has revealed that the inhibitor possesses a hitherto unknown fold for serine proteinase and alpha-amylase inhibitors. Despite its different fold, RBI obeys the standard mechanism observed for most protein inhibitors of serine proteinases and is a strong, competitive inhibitor of bovine trypsin (Ki = 1.2 +/- 0.2 nM). RBI is also a competitive inhibitor of porcine alpha-amylase (Ki = 11 +/- 2 nM) when a disaccharide is used as a substrate of alpha-amylase. However, the inhibition mode becomes complex when larger (> or = 7 saccharide units) alpha-amylase substrates are used. A second saccharide binding site on porcine alpha-amylase may enable larger oligosaccharides to displace RBI from its binding site in an intramolecular reaction.

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Citations

Feb 12, 2004·Biochimica Et Biophysica Acta·Nathalie JugeGary Williamson
Jan 4, 2001·The International Journal of Biochemistry & Cell Biology·J IulekM F Grossi de Sá
Feb 22, 2002·European Journal of Biochemistry·Octávio L FrancoMaria F Grossi-De-Sá
Dec 11, 2002·The Plant Journal : for Cell and Molecular Biology·Eric van der GraaffBeat Keller
Jan 23, 2016·The New Phytologist·Friederike M Grosse-Holz, Renier A L van der Hoorn
Feb 9, 2007·The New Phytologist·Cécile GirardDominique Michaud
Sep 4, 2012·Peptides·E A RogozhinS K Zavriev
Oct 11, 2005·FEBS Letters·Charles S A DaylerMaria F Grossi-de-Sá
May 29, 2000·The Journal of Biological Chemistry·K HiragaK Oda
Dec 23, 2016·Frontiers in Pharmacology·Sandhya Srikanth, Zhong Chen
Jun 20, 1998·Journal of Molecular Biology·S StroblR Glockshuber

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