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Structure and Characterization of Phosphoglucomutase 5 from Atlantic and Baltic Herring-An Inactive Enzyme with

Robert Gustafsson1, Ulrich Eckhard1, Weihua Ye2

  • 1Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-751 24 Uppsala, Sweden.

Biomolecules
|December 8, 2020
PubMed

Insights

Phosphoglucomutase 5 (PGM5) lacks enzymatic activity, unlike its related enzyme PGM1. Structural analysis reveals differences in active-site loops, explaining PGM5's non-enzymatic function and potential roles in protein interactions.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Evolutionary Biology

Background:

  • Phosphoglucomutase 5 (PGM5) is a human protein recognized for its structural role in muscle, lacking known enzymatic activity.
  • PGM5 belongs to the alpha-D-phosphohexomutase family and is evolutionarily linked to the active metabolic enzyme PGM1.
  • PGM5 gene variants are implicated in the ecological adaptation of Atlantic herring (Clupea harengus) to the Baltic Sea environment.

Purpose of the Study:

  • To determine the first crystal structures of PGM5 from Atlantic and Baltic herring.
  • To investigate the structural basis for PGM5's lack of phosphoglucomutase activity.
  • To explore the functional implications of the Ala330Val substitution in Baltic herring PGM5.

Main Methods:

  • X-ray crystallography of PGM5 from Atlantic and Baltic herring.
  • Biochemical assays to test phosphoglucomutase activity.
  • Comparative structural analysis and sequence analysis of PGM5 and PGM1.

Main Results:

  • The crystal structures of Atlantic and Baltic herring PGM5 were determined, revealing high similarity to PGM1.
  • Both PGM5 variants demonstrated no phosphoglucomutase activity, even when complexed with glucose-1-phosphate.
  • Structural comparisons indicated that differences in active-site loops likely account for PGM5's lack of enzymatic function.
  • The Ala330Val substitution, while not affecting structure or biophysical properties, may influence protein-protein interactions due to its surface-exposed location.

Conclusions:

  • PGM5 functions non-enzymatically, with structural differences in active-site loops compared to PGM1 explaining this.
  • The Ala330Val substitution in Baltic herring PGM5 may modulate its interactions with other proteins, potentially relating to adaptation.
  • This study provides structural insights into the functional divergence within the phosphohexomutase family.
Keywords:
adaptationenzyme structureherringphosphoglucomutase 5phosphohexomutase

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