Structural Basis of Nucleotide Selectivity in Pyruvate Kinase

Taguchi, Atsushi; Nakashima, Ryosuke; Nishino, Kunihiko

Journal of Molecular Biology, 2024, 436(18), 168708

Number of Access:418（2025-07-29 15:44 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98167

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Title
Structural Basis of Nucleotide Selectivity in Pyruvate Kinase
Creator
NRID
1000020908686 1000020908686
ORCID
0000-0003-4962-0393 0000-0003-4962-0393
researchmap permalink
atsushi_taguchi atsushi_taguchi
Scopus Author ID
57199647175 57199647175
CreatorName
Taguchi, Atsushi
NRID
1000020379100 1000020379100
researchmap permalink
nakashi nakashi
Scopus Author ID
7005644436 7005644436
CreatorName
Nakashima, Ryosuke
NRID
1000030432438 1000030432438
ORCID
0000-0003-3349-1769 0000-0003-3349-1769
researchmap permalink
read0210124 read0210124
Scopus Author ID
7102938399 7102938399
CreatorName
Nishino, Kunihiko
Subject
ADP
GDP
Glycolysis
Prokaryotic metabolism
X-ray crystallography
Description
Taguchi A., Nakashima R., Nishino K. Structural Basis of Nucleotide Selectivity in Pyruvate Kinase. Journal of Molecular Biology 436, 168708 (2024); https://doi.org/10.1016/j.jmb.2024.168708.
Abstract
Nucleoside triphosphates are indispensable in numerous biological processes, with enzymes involved in their biogenesis playing pivotal roles in cell proliferation. Pyruvate kinase (PYK), commonly regarded as the terminal glycolytic enzyme that generates ATP in tandem with pyruvate, is also capable of synthesizing a wide range of nucleoside triphosphates from their diphosphate precursors. Despite their substrate promiscuity, some PYKs show preference towards specific nucleotides, suggesting an underlying mechanism for differentiating nucleotide bases. However, the thorough characterization of this mechanism has been hindered by the paucity of nucleotide-bound PYK structures. Here, we present crystal structures of Streptococcus pneumoniae PYK in complex with four different nucleotides. These structures facilitate direct comparison of the protein-nucleotide interactions and offer structural insights into its pronounced selectivity for GTP synthesis. Notably, this selectivity is dependent on a sequence motif in the nucleotide recognition site that is widely present among prokaryotic PYKs, particularly in Firmicutes species. We show that pneumococcal cell growth is significantly impaired when expressing a PYK variant with compromised GTP and UTP synthesis activity, underscoring the importance of PYK in maintaining nucleotide homeostasis. Our findings collectively advance our understanding of PYK biochemistry and prokaryotic metabolism.
Publisher
Elsevier B.V.
Source Title
Journal of Molecular Biology
Volume (Issue)
436(18)
Page
168708
Date of Issued
2024-09-15
Language
English
Handle URL
https://hdl.handle.net/11094/98167
PISSN
00222836
eISSN
10898638
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1016/j.jmb.2024.168708
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article