Effects of a Buried Cysteine-To-Serine Mutation on Yeast Triosephosphate Isomerase Structure and Stability

International Journal of Molecular Sciences

Alejandra Hernández-Santoyo⁴  Lenin Domínguez-Ramírez²  César A. Reyes-López⁵  Edith González-Mondragón³  Andrés Hernández-Arana¹ 

[1] Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Iztapalapa 09340, D.F., Mexico;División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Lerma, Lerma de Villada 07360, Mexico; E-Mail:;Instituto de Agroindustrias, Universidad Tecnológica de la Mixteca, Huajuapan de León, Oaxaca 69000, Mexico; E-Mail:;Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, CU México D.F. 04510, Mexico; E-Mail:;Laboratorio de Investigación Bioquímica, Postgrado Institucional en Biomedicina Molecular, ENMyH-Instituto Politécnico Nacional, CP 07320 México, DF, Mexico; E-Mail:

关键词: crystal structure;    molecular dynamics;    Saccharomyces cerevisiae;    stability;    triosephosphate isomerase;   

DOI  :  10.3390/ijms130810010

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.