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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...

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Autores principales: Nagata, Ryuhei, Fujihashi, Masahiro, Sato, Takaaki, Atomi, Haruyuki, Miki, Kunio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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.
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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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