Complexes of Thermoactinomyces vulgaris R-47 alpha-amylase 1 and pullulan model oligossacharides provide new insight into the mechanism for recognizing substrates with alpha-(1,6) glycosidic linkages

FEBS J. 2005 Dec;272(23):6145-53. doi: 10.1111/j.1742-4658.2005.05013.x.

Abstract

Thermoactinomyces vulgaris R-47 alpha-amylase 1 (TVAI) has unique hydrolyzing activities for pullulan with sequence repeats of alpha-(1,4), alpha-(1,4), and alpha-(1,6) glycosidic linkages, as well as for starch. TVAI mainly hydrolyzes alpha-(1,4) glycosidic linkages to produce a panose, but it also hydrolyzes alpha-(1,6) glycosidic linkages with a lesser efficiency. X-ray structures of three complexes comprising an inactive mutant TVAI (D356N or D356N/E396Q) and a pullulan model oligosaccharide (P2; [Glc-alpha-(1,6)-Glc-alpha-(1,4)-Glc-alpha-(1,4)]2 or P5; [Glc-alpha-(1,6)-Glc-alpha-(1,4)-Glc-alpha-(1,4)]5) were determined. The complex D356N/P2 is a mimic of the enzyme/product complex in the main catalytic reaction of TVAI, and a structural comparison with Aspergillus oryzaealpha-amylase showed that the (-) subsites of TVAI are responsible for recognizing both starch and pullulan. D356N/E396Q/P2 and D356N/E396Q/P5 provided models of the enzyme/substrate complex recognizing the alpha-(1,6) glycosidic linkage at the hydrolyzing site. They showed that only subsites -1 and -2 at the nonreducing end of TVAI are effective in the hydrolysis of alpha-(1,6) glycosidic linkages, leading to weak interactions between substrates and the enzyme. Domain N of TVAI is a starch-binding domain acting as an anchor in the catalytic reaction of the enzyme. In this study, additional substrates were also found to bind to domain N, suggesting that domain N also functions as a pullulan-binding domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carbohydrate Sequence
  • Catalytic Domain
  • Crystallography, X-Ray
  • Glucans* / chemistry
  • Glucans* / metabolism
  • Micromonosporaceae* / chemistry
  • Micromonosporaceae* / enzymology
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Multiprotein Complexes
  • Mutagenesis, Site-Directed
  • Oligosaccharides* / chemistry
  • Oligosaccharides* / metabolism
  • Protein Structure, Tertiary*
  • alpha-Amylases / chemistry*
  • alpha-Amylases / genetics
  • alpha-Amylases / metabolism

Substances

  • Bacterial Proteins
  • Glucans
  • Multiprotein Complexes
  • Oligosaccharides
  • pullulan
  • alpha-Amylases