Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite.
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.
Department of Microbiology and Cell Science and Genetic Institute, University of Florida , P.O. Box 110700, Gainesville, Florida 32611-0700, United States.
Jennifer J
JJ
Thiaville
Department of Molecular, Cellular and Developmental Biology, University of Colorado , Boulder, Colorado United States.
Jake
J
Flood
Dalhousie University , 6299 South St., Halifax, NS B3H 4R2, Canada.
Svetlana
S
Yurgel
Department of Microbiology and Cell Science and Genetic Institute, University of Florida , P.O. Box 110700, Gainesville, Florida 32611-0700, United States.
Laurence
L
Prunetti
West Coast Metabolomics Center, UC Davis , Davis, California, United States.
Mona
M
Elbadawi-Sidhu
Department of Microbiology and Cell Science and Genetic Institute, University of Florida , P.O. Box 110700, Gainesville, Florida 32611-0700, United States.
Geoffrey
G
Hutinet
Department of Biological Sciences, Columbia University , New York, New York, United States.
Farhad
F
Forouhar
Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Xinshuai
X
Zhang
Department of Microbiology and Cell Science and Genetic Institute, University of Florida , P.O. Box 110700, Gainesville, Florida 32611-0700, United States.
Venkateswaran
V
Ganesan
Department of Microbiology and Cell Science and Genetic Institute, University of Florida , P.O. Box 110700, Gainesville, Florida 32611-0700, United States.
Patrick
P
Reddy
West Coast Metabolomics Center, UC Davis , Davis, California, United States.|King Abdulaziz University , Biochemistry Department, Jeddah, Saudi Arabia.
Oliver
O
Fiehn
Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
J A
JA
Gerlt
Department of Biological Sciences, Columbia University , New York, New York, United States.
John F
JF
Hunt
Department of Molecular, Cellular and Developmental Biology, University of Colorado , Boulder, Colorado United States.
Shelley D
SD
Copley
Department of Microbiology and Cell Science and Genetic Institute, University of Florida , P.O. Box 110700, Gainesville, Florida 32611-0700, United States.
Valérie
V
de Crécy-Lagard
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D010770:Phosphotransferases