Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite

Jennifer J. Thiaville, Jake Flood, Svetlana Yurgel, Laurence Prunetti, Mona Elbadawi-Sidhu, Geoffrey Hutinet, Farhad Forouhar, Xinshuai Zhang, Venkateswaran Ganesan, Patrick Reddy, Oliver Fiehn, John Alan Gerlt, John F. Hunt, Shelley D. Copley, Valérie De Crécy-Lagard

Research output: Contribution to journalArticle

Abstract

DUF1537 is a novel family of kinases identified by comparative genomic approaches. The family is widespread and found in all sequenced plant genomes and 16% of sequenced bacterial genomes. DUF1537 is not a monofunctional family and contains subgroups that can be separated by phylogenetic and genome neighborhood context analyses. A subset of the DUF1537 proteins is strongly associated by physical clustering and gene fusion with the PdxA2 family, demonstrated here to be a functional paralog of the 4-phosphohydroxy-l-threonine dehydrogenase enzyme (PdxA), a central enzyme in the synthesis of pyridoxal-5′-phosphate (PLP) in proteobacteria. Some members of this DUF1537 subgroup phosphorylate l-4-hydroxythreonine (4HT) into 4-phosphohydroxy-l-threonine (4PHT), the substrate of PdxA, in vitro and in vivo. This provides an alternative route to PLP from the toxic antimetabolite 4HT that can be directly generated from the toxic intermediate glycolaldehyde. Although the kinetic and physical clustering data indicate that these functions in PLP synthesis are not the main roles of the DUF1537-PdxA2 enzymes, genetic and physiological data suggest these side activities function has been maintained in diverse sets of organisms.

Original languageEnglish (US)
Pages (from-to)2304-2311
Number of pages8
JournalACS chemical biology
Volume11
Issue number8
DOIs
StatePublished - Aug 19 2016

Fingerprint

Pyridoxal Phosphate
Poisons
Metabolites
Phosphotransferases
Genes
L-threonine 3-dehydrogenase
Cluster Analysis
Enzymes
Plant Genome
Bacterial Genomes
Antimetabolites
Proteobacteria
Gene Fusion
Threonine
Genome
Fusion reactions
Kinetics
Proteins
Substrates
hydroxythreonine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Thiaville, J. J., Flood, J., Yurgel, S., Prunetti, L., Elbadawi-Sidhu, M., Hutinet, G., ... De Crécy-Lagard, V. (2016). Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite. ACS chemical biology, 11(8), 2304-2311. https://doi.org/10.1021/acschembio.6b00279

Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite. / Thiaville, Jennifer J.; Flood, Jake; Yurgel, Svetlana; Prunetti, Laurence; Elbadawi-Sidhu, Mona; Hutinet, Geoffrey; Forouhar, Farhad; Zhang, Xinshuai; Ganesan, Venkateswaran; Reddy, Patrick; Fiehn, Oliver; Gerlt, John Alan; Hunt, John F.; Copley, Shelley D.; De Crécy-Lagard, Valérie.

In: ACS chemical biology, Vol. 11, No. 8, 19.08.2016, p. 2304-2311.

Research output: Contribution to journalArticle

Thiaville, JJ, Flood, J, Yurgel, S, Prunetti, L, Elbadawi-Sidhu, M, Hutinet, G, Forouhar, F, Zhang, X, Ganesan, V, Reddy, P, Fiehn, O, Gerlt, JA, Hunt, JF, Copley, SD & De Crécy-Lagard, V 2016, 'Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite', ACS chemical biology, vol. 11, no. 8, pp. 2304-2311. https://doi.org/10.1021/acschembio.6b00279
Thiaville JJ, Flood J, Yurgel S, Prunetti L, Elbadawi-Sidhu M, Hutinet G et al. Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite. ACS chemical biology. 2016 Aug 19;11(8):2304-2311. https://doi.org/10.1021/acschembio.6b00279
Thiaville, Jennifer J. ; Flood, Jake ; Yurgel, Svetlana ; Prunetti, Laurence ; Elbadawi-Sidhu, Mona ; Hutinet, Geoffrey ; Forouhar, Farhad ; Zhang, Xinshuai ; Ganesan, Venkateswaran ; Reddy, Patrick ; Fiehn, Oliver ; Gerlt, John Alan ; Hunt, John F. ; Copley, Shelley D. ; De Crécy-Lagard, Valérie. / Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite. In: ACS chemical biology. 2016 ; Vol. 11, No. 8. pp. 2304-2311.
@article{b709f59f5d9149abbbd00b030f755289,
title = "Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite",
abstract = "DUF1537 is a novel family of kinases identified by comparative genomic approaches. The family is widespread and found in all sequenced plant genomes and 16{\%} of sequenced bacterial genomes. DUF1537 is not a monofunctional family and contains subgroups that can be separated by phylogenetic and genome neighborhood context analyses. A subset of the DUF1537 proteins is strongly associated by physical clustering and gene fusion with the PdxA2 family, demonstrated here to be a functional paralog of the 4-phosphohydroxy-l-threonine dehydrogenase enzyme (PdxA), a central enzyme in the synthesis of pyridoxal-5′-phosphate (PLP) in proteobacteria. Some members of this DUF1537 subgroup phosphorylate l-4-hydroxythreonine (4HT) into 4-phosphohydroxy-l-threonine (4PHT), the substrate of PdxA, in vitro and in vivo. This provides an alternative route to PLP from the toxic antimetabolite 4HT that can be directly generated from the toxic intermediate glycolaldehyde. Although the kinetic and physical clustering data indicate that these functions in PLP synthesis are not the main roles of the DUF1537-PdxA2 enzymes, genetic and physiological data suggest these side activities function has been maintained in diverse sets of organisms.",
author = "Thiaville, {Jennifer J.} and Jake Flood and Svetlana Yurgel and Laurence Prunetti and Mona Elbadawi-Sidhu and Geoffrey Hutinet and Farhad Forouhar and Xinshuai Zhang and Venkateswaran Ganesan and Patrick Reddy and Oliver Fiehn and Gerlt, {John Alan} and Hunt, {John F.} and Copley, {Shelley D.} and {De Cr{\'e}cy-Lagard}, Val{\'e}rie",
year = "2016",
month = "8",
day = "19",
doi = "10.1021/acschembio.6b00279",
language = "English (US)",
volume = "11",
pages = "2304--2311",
journal = "ACS Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite

AU - Thiaville, Jennifer J.

AU - Flood, Jake

AU - Yurgel, Svetlana

AU - Prunetti, Laurence

AU - Elbadawi-Sidhu, Mona

AU - Hutinet, Geoffrey

AU - Forouhar, Farhad

AU - Zhang, Xinshuai

AU - Ganesan, Venkateswaran

AU - Reddy, Patrick

AU - Fiehn, Oliver

AU - Gerlt, John Alan

AU - Hunt, John F.

AU - Copley, Shelley D.

AU - De Crécy-Lagard, Valérie

PY - 2016/8/19

Y1 - 2016/8/19

N2 - DUF1537 is a novel family of kinases identified by comparative genomic approaches. The family is widespread and found in all sequenced plant genomes and 16% of sequenced bacterial genomes. DUF1537 is not a monofunctional family and contains subgroups that can be separated by phylogenetic and genome neighborhood context analyses. A subset of the DUF1537 proteins is strongly associated by physical clustering and gene fusion with the PdxA2 family, demonstrated here to be a functional paralog of the 4-phosphohydroxy-l-threonine dehydrogenase enzyme (PdxA), a central enzyme in the synthesis of pyridoxal-5′-phosphate (PLP) in proteobacteria. Some members of this DUF1537 subgroup phosphorylate l-4-hydroxythreonine (4HT) into 4-phosphohydroxy-l-threonine (4PHT), the substrate of PdxA, in vitro and in vivo. This provides an alternative route to PLP from the toxic antimetabolite 4HT that can be directly generated from the toxic intermediate glycolaldehyde. Although the kinetic and physical clustering data indicate that these functions in PLP synthesis are not the main roles of the DUF1537-PdxA2 enzymes, genetic and physiological data suggest these side activities function has been maintained in diverse sets of organisms.

AB - DUF1537 is a novel family of kinases identified by comparative genomic approaches. The family is widespread and found in all sequenced plant genomes and 16% of sequenced bacterial genomes. DUF1537 is not a monofunctional family and contains subgroups that can be separated by phylogenetic and genome neighborhood context analyses. A subset of the DUF1537 proteins is strongly associated by physical clustering and gene fusion with the PdxA2 family, demonstrated here to be a functional paralog of the 4-phosphohydroxy-l-threonine dehydrogenase enzyme (PdxA), a central enzyme in the synthesis of pyridoxal-5′-phosphate (PLP) in proteobacteria. Some members of this DUF1537 subgroup phosphorylate l-4-hydroxythreonine (4HT) into 4-phosphohydroxy-l-threonine (4PHT), the substrate of PdxA, in vitro and in vivo. This provides an alternative route to PLP from the toxic antimetabolite 4HT that can be directly generated from the toxic intermediate glycolaldehyde. Although the kinetic and physical clustering data indicate that these functions in PLP synthesis are not the main roles of the DUF1537-PdxA2 enzymes, genetic and physiological data suggest these side activities function has been maintained in diverse sets of organisms.

UR - http://www.scopus.com/inward/record.url?scp=84975773123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975773123&partnerID=8YFLogxK

U2 - 10.1021/acschembio.6b00279

DO - 10.1021/acschembio.6b00279

M3 - Article

VL - 11

SP - 2304

EP - 2311

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 8

ER -