The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase
In a previous phylogenetic study of the family of pyruvate kinase, we found one cluster with Glu117 and another with Lys117. Those sequences with Glu117 have Thr113 and are K+-dependent, whereas those with Lys117 have Leu113 and are K+-independent. The carbonyl oxygen of Thr113 is one of the residue...
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doaj-bcdb47b62c0a42ae8b8bb054b00e6dff2020-11-24T22:14:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-12-011512222142222610.3390/ijms151222214ijms151222214The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate KinaseLeticia Ramírez-Silva0Carlos Guerrero-Mendiola1Nallely Cabrera2Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 Distrito Federal, MexicoDepartamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 Distrito Federal, MexicoDepartamento de Bioquímica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Distrito Federal, MexicoIn a previous phylogenetic study of the family of pyruvate kinase, we found one cluster with Glu117 and another with Lys117. Those sequences with Glu117 have Thr113 and are K+-dependent, whereas those with Lys117 have Leu113 and are K+-independent. The carbonyl oxygen of Thr113 is one of the residues that coordinate K+ in the active site. Even though the side chain of Thr113 does not participate in binding K+, the strict co-evolution between position 117 and 113 suggests that T113 may be the result of the evolutionary pressure to maintain the selectivity of pyruvate kinase activity for K+. Thus, we explored if the replacement of Thr113 by Leu alters the characteristics of the K+ binding site. We found that the polarity of the residue 113 is central in the partition of K+ into its site and that the substitution of Thr for Leu changes the ion selectivity for the monovalent cation with minor changes in the binding of the substrates. Therefore, Thr113 is instrumental in the selectivity of pyruvate kinase for K+.http://www.mdpi.com/1422-0067/15/12/22214pyruvate kinaseK+ion selectivitymonovalent cationhydrophobicitysite-directed mutagenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leticia Ramírez-Silva Carlos Guerrero-Mendiola Nallely Cabrera |
spellingShingle |
Leticia Ramírez-Silva Carlos Guerrero-Mendiola Nallely Cabrera The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase International Journal of Molecular Sciences pyruvate kinase K+ ion selectivity monovalent cation hydrophobicity site-directed mutagenesis |
author_facet |
Leticia Ramírez-Silva Carlos Guerrero-Mendiola Nallely Cabrera |
author_sort |
Leticia Ramírez-Silva |
title |
The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase |
title_short |
The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase |
title_full |
The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase |
title_fullStr |
The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase |
title_full_unstemmed |
The Importance of Polarity in the Evolution of the K+ Binding Site of Pyruvate Kinase |
title_sort |
importance of polarity in the evolution of the k+ binding site of pyruvate kinase |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2014-12-01 |
description |
In a previous phylogenetic study of the family of pyruvate kinase, we found one cluster with Glu117 and another with Lys117. Those sequences with Glu117 have Thr113 and are K+-dependent, whereas those with Lys117 have Leu113 and are K+-independent. The carbonyl oxygen of Thr113 is one of the residues that coordinate K+ in the active site. Even though the side chain of Thr113 does not participate in binding K+, the strict co-evolution between position 117 and 113 suggests that T113 may be the result of the evolutionary pressure to maintain the selectivity of pyruvate kinase activity for K+. Thus, we explored if the replacement of Thr113 by Leu alters the characteristics of the K+ binding site. We found that the polarity of the residue 113 is central in the partition of K+ into its site and that the substitution of Thr for Leu changes the ion selectivity for the monovalent cation with minor changes in the binding of the substrates. Therefore, Thr113 is instrumental in the selectivity of pyruvate kinase for K+. |
topic |
pyruvate kinase K+ ion selectivity monovalent cation hydrophobicity site-directed mutagenesis |
url |
http://www.mdpi.com/1422-0067/15/12/22214 |
work_keys_str_mv |
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