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Effects of a Buried Cysteine-To-Serine Mutation on Yeast Triosephosphate Isomerase Structure and Stability
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, CU México D.F. 04510, Mexico
División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Lerma, Lerma de Villada 07360, Mexico
Laboratorio de Investigación Bioquímica, Postgrado Institucional en Biomedicina Molecular, ENMyH-Instituto Politécnico Nacional, CP 07320 México, DF, Mexico
Instituto de Agroindustrias, Universidad Tecnológica de la Mixteca, Huajuapan de León, Oaxaca 69000, Mexico
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Iztapalapa 09340, D.F., Mexico
* Authors to whom correspondence should be addressed.
Received: 4 June 2012; in revised form: 24 July 2012 / Accepted: 26 July 2012 / Published: 10 August 2012
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: crystal structure; molecular dynamics; Saccharomyces cerevisiae; stability; triosephosphate isomerase
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Hernández-Santoyo, A.; Domínguez-Ramírez, L.; Reyes-López, C.A.; González-Mondragón, E.; Hernández-Arana, A.; Rodríguez-Romero, A. Effects of a Buried Cysteine-To-Serine Mutation on Yeast Triosephosphate Isomerase Structure and Stability. Int. J. Mol. Sci. 2012, 13, 10010-10021.
Hernández-Santoyo A, Domínguez-Ramírez L, Reyes-López CA, González-Mondragón E, Hernández-Arana A, Rodríguez-Romero A. Effects of a Buried Cysteine-To-Serine Mutation on Yeast Triosephosphate Isomerase Structure and Stability. International Journal of Molecular Sciences. 2012; 13(8):10010-10021.
Hernández-Santoyo, Alejandra; Domínguez-Ramírez, Lenin; Reyes-López, César A.; González-Mondragón, Edith; Hernández-Arana, Andrés; Rodríguez-Romero, Adela. 2012. "Effects of a Buried Cysteine-To-Serine Mutation on Yeast Triosephosphate Isomerase Structure and Stability." Int. J. Mol. Sci. 13, no. 8: 10010-10021.