Structural analysis of the TPI-Manchester, a thermolabile variant of human triosephosphate isomerase

Arch Biochem Biophys. 2024 Nov:761:110156. doi: 10.1016/j.abb.2024.110156. Epub 2024 Sep 17.

Abstract

Human triosephosphate isomerase G122R, also known as TPI-Manchester, is a thermolabile variant detected in a screening of more than 3400 individuals from a population in Ann Arbor, Michigan. Here, the crystallographic structure of G122R was solved to determine the molecular basis of its thermal stability. Structural analysis revealed an increase in the flexibility of residues at the dimer interface, even though R122 is about 20 Å away, suggesting that long-range electrostatic interactions may play a key role in the mutation effect.

Keywords: Flexibility; Stability; Triosephosphate isomerase deficiency; X-ray crystallization.

MeSH terms

  • Crystallography, X-Ray
  • Enzyme Stability*
  • Humans
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Protein Multimerization
  • Triose-Phosphate Isomerase* / chemistry
  • Triose-Phosphate Isomerase* / genetics
  • Triose-Phosphate Isomerase* / metabolism

Substances

  • Triose-Phosphate Isomerase