Format

Send to:

Choose Destination
See comment in PubMed Commons below
Int J Mol Sci. 2012;13(8):10010-21. doi: 10.3390/ijms130810010. Epub 2012 Aug 10.

Effects of a buried cysteine-to-serine mutation on yeast triosephosphate isomerase structure and stability.

Author information

  • 1Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, CU México D.F. 04510, Mexico; E-Mail: hersan@unam.mx.

Abstract

All the members of the triosephosphate isomerase (TIM) family possess a cystein residue (Cys126) located near the catalytically essential Glu165. The evolutionarily conserved Cys126, however, does not seem to play a significant role in the catalytic activity. On the other hand, substitution of this residue by other amino acid residues destabilizes the dimeric enzyme, especially when Cys is replaced by Ser. In trying to assess the origin of this destabilization we have determined the crystal structure of Saccharomyces cerevisiae TIM (ScTIM) at 1.86 Å resolution in the presence of PGA, which is only bound to one subunit. Comparisons of the wild type and mutant structures reveal that a change in the orientation of the Ser hydroxyl group, with respect to the Cys sulfhydryl group, leads to penetration of water molecules and apparent destabilization of residues 132-138. The latter results were confirmed by means of Molecular Dynamics, which showed that this region, in the mutated enzyme, collapses at about 70 ns.

KEYWORDS:

Saccharomyces cerevisiae; crystal structure; molecular dynamics; stability; triosephosphate isomerase

PMID:
22949845
[PubMed - indexed for MEDLINE]
PMCID:
PMC3431843
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
    Loading ...
    Write to the Help Desk