Specific inhibition of insect α-amylases: Yellow meal worm α-amylase in complex with the Amaranth α-amylase inhibitor at 2.0 Å resolution

Pedro José Barbosa Pereira, Valentin Lozanov, András Patthy, Robert Huber, Wolfram Bode, Sándor Pongor, Stefan Strobl

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Background: α-Amylases constitute a family of enzymes that catalyze the hydrolysis of α-D-(1,4)-glucan linkages in starch and related polysaccharides. The Amaranth α-amylase inhibitor (AAI) specifically inhibits α-amylases from insects, but not from mammalian sources. AAI is the smallest proteinaceous α-amylase inhibitor described so far and has no known homologs in the sequence databases. Its mode of inhibition of α-amylases was unknown until now. Results: The crystal structure of yellow meal worm α- amylase (TMA) in complex with AAI was determined at 2.0 Å resolution. The overall fold of AAI, its three-stranded twisted β 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 α-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 α-amylases. Due to its unique specificity towards insect α-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.

Original languageEnglish
Pages (from-to)1079-1088
Number of pages10
JournalStructure
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 1999

    Fingerprint

Keywords

  • Amaranthus hypochondriacus
  • Insect α-amylase inhibitor
  • Knottin
  • X-ray structure
  • Yellow meal worm

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this