The effect of a Pro28Thr point mutation on the local structure and stability of human galactokinase enzyme-a theoretical study

Balázs Jójárt, Milán Szori, Róbert Izsák, István Marsi, Aranka László, Imre G. Csizmadia, Béla Viskolcz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Galactokinase is responsible for the phosphorylation of α-d-galactose, which is an important step in the metabolism of the latter. Malfunctioning of galactokinase due to a single point mutation causes cataracts and, in serious cases, blindness. This paper reports a study of the Pro 28Thr point mutation using a variety of theories including molecular dynamics (MD), MM-PBSA/GBSA calculations and AIM analysis. Altered H-bonding networks were detected based on geometric and electron density criteria that resulted in local unfolding of the β-sheet secondary structure. Another consequence was the decrease in stability (5-7 kcal mol-1) around this region, as confirmed by ΔGbind calculations for the extracted part of the whole system. Local unfolding was verified by several other MD simulations performed with different duration, initial velocities and force field. Based on the results, we propose a possible mechanism for the unfolding caused by the Pro28Thr point mutation. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)2639-2649
Number of pages11
JournalJournal of Molecular Modeling
Volume17
Issue number10
DOIs
Publication statusPublished - Oct 1 2011

Keywords

  • AIM
  • Human galactokinase
  • Local unfolding
  • MMPBSA/GBSA
  • Molecular dynamics
  • β-sheet stability

ASJC Scopus subject areas

  • Catalysis
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Computational Theory and Mathematics
  • Inorganic Chemistry

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