BACKGROUND: alpha-Amylases constitute a family of enzymes that catalyze the hydrolysis of alpha-D-(1,4)-glucan linkages in starch and related polysaccharides. The Amaranth alpha-amylase inhibitor (AAI) specifically inhibits alpha-amylases from insects, but not from mammalian sources. AAI is the smallest proteinaceous alpha-amylase inhibitor described so far and has no known homologs in the sequence databases. Its mode of inhibition of alpha-amylases was unknown until now. RESULTS: The crystal structure of yellow meal worm alpha-amylase (TMA) in complex with AAI was determined at 2.0 A resolution. The overall fold of AAI, its three-stranded twisted beta sheet and the topology of its disulfide bonds identify it as a knottin-like protein. The inhibitor binds into the active-site groove of TMA, blocking the central four sugar-binding subsites. Residues from two AAI segments target the active-site residues of TMA. A comparison of the TMA-AAI complex with a modeled complex between porcine pancreatic alpha-amylase (PPA) and AAI identified six hydrogen bonds that can be formed only in the TMA-AAI complex. CONCLUSIONS: The binding of AAI to TMA presents a new inhibition mode for alpha-amylases. Due to its unique specificity towards insect alpha-amylases, AAI might represent a valuable tool for protecting crop plants from predatory insects. The close structural homology between AAI and 'knottins' opens new perspectives for the engineering of various novel activities onto the small scaffold of this group of proteins.
Specific inhibition of insect alpha-amylases: yellow meal worm alpha-amylase in complex with the amaranth alpha-amylase inhibitor at 2.0 A resolution.,Pereira PJ, Lozanov V, Patthy A, Huber R, Bode W, Pongor S, Strobl S Structure. 1999 Sep 15;7(9):1079-88. PMID:10508777
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Pereira PJ, Lozanov V, Patthy A, Huber R, Bode W, Pongor S, Strobl S. Specific inhibition of insect alpha-amylases: yellow meal worm alpha-amylase in complex with the amaranth alpha-amylase inhibitor at 2.0 A resolution. Structure. 1999 Sep 15;7(9):1079-88. PMID:10508777