Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins

EF-hands are Ca2+ binding motifs that are widely distributed throughout the entire living organism kingdom. At present, relatively little is known at a quantum mechanical level about the mechanisms that allow Ca 2+ to be recognized specifically by EF-hands and to induce a conformational switch from...

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Autores principales:	Biekofsky, Rodolfo Roberto, Turjanski, Adrián Gustavo, Estrin, Dario Ariel
Publicado:	2004
Materias:	Calcium Conformations Hydrophobicity Molecular structure Nuclear magnetic resonance spectroscopy Proteins Binding motifs Chemical shift Metal binding Biochemical engineering amide calcium ion EF hand protein isoleucine protein unclassified drug ab initio calculation article beta sheet binding site calcium binding calcium binding motif conformational transition ef hand domain hydrogen bond hydrophobicity metal binding nitrogen nuclear magnetic resonance pi polarization polarization priority journal protein conformation protein domain protein interaction protein motif quantum mechanics Amino Acid Motifs Amino Acid Sequence Calmodulin Holoenzymes Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Nitrogen Isotopes Protein Conformation Protein Structure, Tertiary
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v43_n21_p6554_Biekofsky http://hdl.handle.net/20.500.12110/paper_00062960_v43_n21_p6554_Biekofsky
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_00062960_v43_n21_p6554_Biekofsky2023-06-08T14:30:40Z Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins Biekofsky, Rodolfo Roberto Turjanski, Adrián Gustavo Estrin, Dario Ariel Calcium Conformations Hydrophobicity Molecular structure Nuclear magnetic resonance spectroscopy Proteins Binding motifs Chemical shift Metal binding Biochemical engineering amide calcium ion EF hand protein isoleucine protein unclassified drug ab initio calculation article beta sheet binding site calcium binding calcium binding motif conformational transition ef hand domain hydrogen bond hydrophobicity metal binding nitrogen nuclear magnetic resonance pi polarization polarization priority journal protein conformation protein domain protein interaction protein motif quantum mechanics Amino Acid Motifs Amino Acid Sequence Calcium Calmodulin Holoenzymes Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Nitrogen Isotopes Protein Conformation Protein Structure, Tertiary EF-hands are Ca2+ binding motifs that are widely distributed throughout the entire living organism kingdom. At present, relatively little is known at a quantum mechanical level about the mechanisms that allow Ca 2+ to be recognized specifically by EF-hands and to induce a conformational switch from a compact ("closed") conformation to an "open" state that exposes a large patch of hydrophobic residues. Here, we present a study of NMR 15N chemical shifts based on ab initio quantum mechanical calculations carried out on a minimalist model system linking both Ca2+ binding sites across the β-sheet of an EF-hand domain. Calculated and experimentally determined chemical shift changes are correlated with structural changes induced upon metal binding. The effect of Ca2+ binding on these 15N shifts can be dissected into two main contributions: one from π-polarization of β-sheet amide groups and the other from rotation of an isoleucine side chain. By correlating this description with experimental evidence, different polarization states for the β-sheet amide groups were identified and linked to the overall conformation of different EF-hand domains. When all four β-sheet amide groups are polarized, the ab initio calculations in our model indicate a cooperative stabilization effect due to the establishment of a circular network of donor-acceptor interactions connecting the two Ca2+ ions across the β-sheet. The emerging hypothesis from our analysis is that this cooperative network of interactions is essential for stabilizing the "open" conformation of an EF-hand domain. Fil:Biekofsky, R.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Turjanski, A.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v43_n21_p6554_Biekofsky http://hdl.handle.net/20.500.12110/paper_00062960_v43_n21_p6554_Biekofsky
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Calcium Conformations Hydrophobicity Molecular structure Nuclear magnetic resonance spectroscopy Proteins Binding motifs Chemical shift Metal binding Biochemical engineering amide calcium ion EF hand protein isoleucine protein unclassified drug ab initio calculation article beta sheet binding site calcium binding calcium binding motif conformational transition ef hand domain hydrogen bond hydrophobicity metal binding nitrogen nuclear magnetic resonance pi polarization polarization priority journal protein conformation protein domain protein interaction protein motif quantum mechanics Amino Acid Motifs Amino Acid Sequence Calcium Calmodulin Holoenzymes Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Nitrogen Isotopes Protein Conformation Protein Structure, Tertiary
spellingShingle	Calcium Conformations Hydrophobicity Molecular structure Nuclear magnetic resonance spectroscopy Proteins Binding motifs Chemical shift Metal binding Biochemical engineering amide calcium ion EF hand protein isoleucine protein unclassified drug ab initio calculation article beta sheet binding site calcium binding calcium binding motif conformational transition ef hand domain hydrogen bond hydrophobicity metal binding nitrogen nuclear magnetic resonance pi polarization polarization priority journal protein conformation protein domain protein interaction protein motif quantum mechanics Amino Acid Motifs Amino Acid Sequence Calcium Calmodulin Holoenzymes Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Nitrogen Isotopes Protein Conformation Protein Structure, Tertiary Biekofsky, Rodolfo Roberto Turjanski, Adrián Gustavo Estrin, Dario Ariel Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins
topic_facet	Calcium Conformations Hydrophobicity Molecular structure Nuclear magnetic resonance spectroscopy Proteins Binding motifs Chemical shift Metal binding Biochemical engineering amide calcium ion EF hand protein isoleucine protein unclassified drug ab initio calculation article beta sheet binding site calcium binding calcium binding motif conformational transition ef hand domain hydrogen bond hydrophobicity metal binding nitrogen nuclear magnetic resonance pi polarization polarization priority journal protein conformation protein domain protein interaction protein motif quantum mechanics Amino Acid Motifs Amino Acid Sequence Calcium Calmodulin Holoenzymes Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Nitrogen Isotopes Protein Conformation Protein Structure, Tertiary
description	EF-hands are Ca2+ binding motifs that are widely distributed throughout the entire living organism kingdom. At present, relatively little is known at a quantum mechanical level about the mechanisms that allow Ca 2+ to be recognized specifically by EF-hands and to induce a conformational switch from a compact ("closed") conformation to an "open" state that exposes a large patch of hydrophobic residues. Here, we present a study of NMR 15N chemical shifts based on ab initio quantum mechanical calculations carried out on a minimalist model system linking both Ca2+ binding sites across the β-sheet of an EF-hand domain. Calculated and experimentally determined chemical shift changes are correlated with structural changes induced upon metal binding. The effect of Ca2+ binding on these 15N shifts can be dissected into two main contributions: one from π-polarization of β-sheet amide groups and the other from rotation of an isoleucine side chain. By correlating this description with experimental evidence, different polarization states for the β-sheet amide groups were identified and linked to the overall conformation of different EF-hand domains. When all four β-sheet amide groups are polarized, the ab initio calculations in our model indicate a cooperative stabilization effect due to the establishment of a circular network of donor-acceptor interactions connecting the two Ca2+ ions across the β-sheet. The emerging hypothesis from our analysis is that this cooperative network of interactions is essential for stabilizing the "open" conformation of an EF-hand domain.
author	Biekofsky, Rodolfo Roberto Turjanski, Adrián Gustavo Estrin, Dario Ariel
author_facet	Biekofsky, Rodolfo Roberto Turjanski, Adrián Gustavo Estrin, Dario Ariel
author_sort	Biekofsky, Rodolfo Roberto
title	Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins
title_short	Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins
title_full	Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins
title_fullStr	Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins
title_full_unstemmed	Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins
title_sort	ab initio study of nmr 15n chemical shift differences induced by ca2+ binding to ef-hand proteins
publishDate	2004
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v43_n21_p6554_Biekofsky http://hdl.handle.net/20.500.12110/paper_00062960_v43_n21_p6554_Biekofsky
work_keys_str_mv	AT biekofskyrodolforoberto abinitiostudyofnmr15nchemicalshiftdifferencesinducedbyca2bindingtoefhandproteins AT turjanskiadriangustavo abinitiostudyofnmr15nchemicalshiftdifferencesinducedbyca2bindingtoefhandproteins AT estrindarioariel abinitiostudyofnmr15nchemicalshiftdifferencesinducedbyca2bindingtoefhandproteins
_version_	1768542344762621952

Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins

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