Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2
Abstract Histidine residues contribute to numerous molecular interactions, owing to their structure with the ionizable aromatic side chain with pKa close to the physiological pH. Herein, we studied how the two histidine residues, His115 and His160 of the catalytic subunit of human protein kinase CK2...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51905-y |
| _version_ | 1797350020258725888 |
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| author | Maria Winiewska-Szajewska Daniel Paprocki Ewa Marzec Jarosław Poznański |
| author_facet | Maria Winiewska-Szajewska Daniel Paprocki Ewa Marzec Jarosław Poznański |
| author_sort | Maria Winiewska-Szajewska |
| collection | DOAJ |
| description | Abstract Histidine residues contribute to numerous molecular interactions, owing to their structure with the ionizable aromatic side chain with pKa close to the physiological pH. Herein, we studied how the two histidine residues, His115 and His160 of the catalytic subunit of human protein kinase CK2, affect the binding of the halogenated heterocyclic ligands at the ATP-binding site. Thermodynamic studies on the interaction between five variants of hCK2α (WT protein and four histidine mutants) and three ionizable bromo-benzotriazoles and their conditionally non-ionizable benzimidazole counterparts were performed with nanoDSF, MST, and ITC. The results allowed us to identify the contribution of interactions involving the particular histidine residues to ligand binding. We showed that despite the well-documented hydrogen bonding/salt bridge formation dragging the anionic ligands towards Lys68, the protonated His160 also contributes to the binding of such ligands by long-range electrostatic interactions. Simultaneously, His 115 indirectly affects ligand binding, placing the hinge region in open/closed conformations. |
| first_indexed | 2024-03-08T12:38:45Z |
| format | Article |
| id | doaj.art-c3c4050e122a47c8850d48110255185f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T12:38:45Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c3c4050e122a47c8850d48110255185f2024-01-21T12:19:51ZengNature PortfolioScientific Reports2045-23222024-01-0114111410.1038/s41598-024-51905-yEffect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2Maria Winiewska-Szajewska0Daniel Paprocki1Ewa Marzec2Jarosław Poznański3Institute of Biochemistry and Biophysics PASInstitute of Biochemistry and Biophysics PASInstitute of Biochemistry and Biophysics PASInstitute of Biochemistry and Biophysics PASAbstract Histidine residues contribute to numerous molecular interactions, owing to their structure with the ionizable aromatic side chain with pKa close to the physiological pH. Herein, we studied how the two histidine residues, His115 and His160 of the catalytic subunit of human protein kinase CK2, affect the binding of the halogenated heterocyclic ligands at the ATP-binding site. Thermodynamic studies on the interaction between five variants of hCK2α (WT protein and four histidine mutants) and three ionizable bromo-benzotriazoles and their conditionally non-ionizable benzimidazole counterparts were performed with nanoDSF, MST, and ITC. The results allowed us to identify the contribution of interactions involving the particular histidine residues to ligand binding. We showed that despite the well-documented hydrogen bonding/salt bridge formation dragging the anionic ligands towards Lys68, the protonated His160 also contributes to the binding of such ligands by long-range electrostatic interactions. Simultaneously, His 115 indirectly affects ligand binding, placing the hinge region in open/closed conformations.https://doi.org/10.1038/s41598-024-51905-y |
| spellingShingle | Maria Winiewska-Szajewska Daniel Paprocki Ewa Marzec Jarosław Poznański Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2 Scientific Reports |
| title | Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2 |
| title_full | Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2 |
| title_fullStr | Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2 |
| title_full_unstemmed | Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2 |
| title_short | Effect of histidine protonation state on ligand binding at the ATP-binding site of human protein kinase CK2 |
| title_sort | effect of histidine protonation state on ligand binding at the atp binding site of human protein kinase ck2 |
| url | https://doi.org/10.1038/s41598-024-51905-y |
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