IMASL   20939
INSTITUTO DE MATEMATICA APLICADA DE SAN LUIS "PROF. EZIO MARCHI"
Unidad Ejecutora - UE
artículos
Título:
Assessing the fractions of tautomeric forms of the imidazole ring of histidine in proteins as a function of pH
Autor/es:
J.A. VILA, Y.A. ARNAUTOVA, Y. VOROBJEV AND H.A. SCHERAGA
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Año: 2011 vol. 108 p. 5602 - 5607
ISSN:
0027-8424
Resumen:
A method is proposed to determine the fraction of the tautomeric
forms of the imidazole ring of histidine in proteins as a function
of pH, provided that the observed 13C¥ã and 13C¥ä2 chemical shifts
and the protein structure, or the fraction of H© form, are known.
This method is based on the use of quantum chemical methods to
compute the 13C NMR shieldings of all the imidazole ring carbons
(13C¥ã, 13C¥ä2, and 13Cϵ1) for each of the two tautomers, N¥ä1-H and
Nϵ2-H, and the protonated form, H©, of histidine. This methodology
enabled us (i) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement13C¥ã and 13C¥ä2 chemical shifts
and the protein structure, or the fraction of H© form, are known.
This method is based on the use of quantum chemical methods to
compute the 13C NMR shieldings of all the imidazole ring carbons
(13C¥ã, 13C¥ä2, and 13Cϵ1) for each of the two tautomers, N¥ä1-H and
Nϵ2-H, and the protonated form, H©, of histidine. This methodology
enabled us (i) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement© form, are known.
This method is based on the use of quantum chemical methods to
compute the 13C NMR shieldings of all the imidazole ring carbons
(13C¥ã, 13C¥ä2, and 13Cϵ1) for each of the two tautomers, N¥ä1-H and
Nϵ2-H, and the protonated form, H©, of histidine. This methodology
enabled us (i) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement13C NMR shieldings of all the imidazole ring carbons
(13C¥ã, 13C¥ä2, and 13Cϵ1) for each of the two tautomers, N¥ä1-H and
Nϵ2-H, and the protonated form, H©, of histidine. This methodology
enabled us (i) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement13C¥ã, 13C¥ä2, and 13Cϵ1) for each of the two tautomers, N¥ä1-H and
Nϵ2-H, and the protonated form, H©, of histidine. This methodology
enabled us (i) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreementϵ2-H, and the protonated form, H©, of histidine. This methodology
enabled us (i) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreementi) to determine the fraction of all the tautomeric forms
of histidine for eight proteins for which the 13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement13C¥ã and 13C¥ä2 chemical
shifts had been determined in solution in the pH range of 3.2 to
7.5 and (ii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreementii) to estimate the fraction of tautomeric forms of eight
histidine-containing dipeptide crystals for which the chemical shifts
had been determined by solid-state 13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement13C NMR. Our results for proteins
indicate that the protonated form is the most populated one,
whereas the distribution of the tautomeric forms for the imidazole
ring varies significantly among different histidines in the same protein,
reflecting the importance of the environment of the histidines
in determining the tautomeric forms. In addition, for ¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement¡70% of the
neutral histidine-containing dipeptides, the method leads to fairly
good agreement between the calculated and the experimental
tautomeric form. Coexistence of different tautomeric forms in the
same crystal structure may explain the remaining 30% of disagreement