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Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants
Almost all kinases utilize ATP as their phosphate donor, while a few kinases utilize pyrophosphate (PPi) instead. PPi-dependent kinases are often homologous to their ATP-dependent counterparts, but determinants of their different donor specificities remain unclear. We identify a PPi-dependent member...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931981/ https://www.ncbi.nlm.nih.gov/pubmed/29720581 http://dx.doi.org/10.1038/s41467-018-04201-z |
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author | Nagata, Ryuhei Fujihashi, Masahiro Sato, Takaaki Atomi, Haruyuki Miki, Kunio |
author_facet | Nagata, Ryuhei Fujihashi, Masahiro Sato, Takaaki Atomi, Haruyuki Miki, Kunio |
author_sort | Nagata, Ryuhei |
collection | PubMed |
description | Almost all kinases utilize ATP as their phosphate donor, while a few kinases utilize pyrophosphate (PPi) instead. PPi-dependent kinases are often homologous to their ATP-dependent counterparts, but determinants of their different donor specificities remain unclear. We identify a PPi-dependent member of the ribokinase family, which differs from known PPi-dependent kinases, and elucidate its PPi-binding mode based on the crystal structures. Structural comparison and sequence alignment reveal five important residues: three basic residues specifically recognizing PPi and two large hydrophobic residues occluding a part of the ATP-binding pocket. Two of the three basic residues adapt a conserved motif of the ribokinase family for the PPi binding. Using these five key residues as a signature pattern, we discover additional PPi-specific members of the ribokinase family, and thus conclude that these residues are the determinants of PPi-specific binding. Introduction of these residues may enable transformation of ATP-dependent ribokinase family members into PPi-dependent enzymes. |
format | Online Article Text |
id | pubmed-5931981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59319812018-05-07 Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants Nagata, Ryuhei Fujihashi, Masahiro Sato, Takaaki Atomi, Haruyuki Miki, Kunio Nat Commun Article Almost all kinases utilize ATP as their phosphate donor, while a few kinases utilize pyrophosphate (PPi) instead. PPi-dependent kinases are often homologous to their ATP-dependent counterparts, but determinants of their different donor specificities remain unclear. We identify a PPi-dependent member of the ribokinase family, which differs from known PPi-dependent kinases, and elucidate its PPi-binding mode based on the crystal structures. Structural comparison and sequence alignment reveal five important residues: three basic residues specifically recognizing PPi and two large hydrophobic residues occluding a part of the ATP-binding pocket. Two of the three basic residues adapt a conserved motif of the ribokinase family for the PPi binding. Using these five key residues as a signature pattern, we discover additional PPi-specific members of the ribokinase family, and thus conclude that these residues are the determinants of PPi-specific binding. Introduction of these residues may enable transformation of ATP-dependent ribokinase family members into PPi-dependent enzymes. Nature Publishing Group UK 2018-05-02 /pmc/articles/PMC5931981/ /pubmed/29720581 http://dx.doi.org/10.1038/s41467-018-04201-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Nagata, Ryuhei Fujihashi, Masahiro Sato, Takaaki Atomi, Haruyuki Miki, Kunio Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
title | Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
title_full | Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
title_fullStr | Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
title_full_unstemmed | Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
title_short | Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
title_sort | identification of a pyrophosphate-dependent kinase and its donor selectivity determinants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931981/ https://www.ncbi.nlm.nih.gov/pubmed/29720581 http://dx.doi.org/10.1038/s41467-018-04201-z |
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