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Related Experiment Videos

The (betaalpha)(8) glycosidases: sequence and structure analyses suggest distant evolutionary relationships.

N Nagano1, C T Porter, J M Thornton

  • 1Biomolecular Structure and Modelling Group, Biochemistry & Molecular Biology Department, University College London, Gower Street, London WC1E 6BT, UK.

Protein Engineering
|December 14, 2001
PubMed
Summary

Glycosidase enzymes with TIM barrel folds were clustered into four groups (S1-S4) based on sequence and structure. Evolutionary relationships were explored, revealing distant connections between S1/S2 and S3/S4 enzyme families.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Evolutionary Biology

Background:

  • Glycosidases are enzymes crucial for carbohydrate metabolism.
  • Many glycosidases share a common TIM barrel protein fold.
  • Understanding their evolutionary relationships is complex due to conserved structures.

Purpose of the Study:

  • To investigate the evolutionary relationships among different glycosidase sequence families.
  • To explore the structural and functional diversity within the TIM barrel fold.
  • To compare newly identified clusters with existing glycosidase classifications.

Main Methods:

  • Comprehensive sequence and structure comparisons were performed.
  • Four distinct clusters (S1-S4) of glycosidases were generated.

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  • PSI-BLAST profiles and multiple tertiary structure alignments were utilized.

    • Main Results:

    • Cluster S1 contains alpha-amylase related enzymes (retention mechanism).
    • Cluster S2 includes glucosidases (retention) and beta-amylases (inversion).
    • Cluster S3 comprises chitinases and hevamine-type enzymes (retention).
    • Cluster S4 consists of chitobiase (retention).
    • Distant evolutionary relationships were suggested between S1/S2 and S3/S4.
    • Enzymes in S3 and S4 act on N-acetylated substrates.

    Conclusions:

    • The TIM barrel fold is present in at least nine distinct glycosidase sequence families.
    • Sequence and structure analyses reveal four major clusters of glycosidases.
    • Untangling distant evolutionary relationships within ubiquitous folds like the TIM barrel presents significant challenges.