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Title: Assignment of function to a domain of unknown function: DUF1537 is a new kinase family in catabolic pathways for acid sugars

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [1];  [2];  [1];  [3];  [2];  [1];  [4];  [4];  [3];  [2];  [1]
  1. Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)
  2. Albert Einstein College of Medicine, Bronx, NY (United States)
  3. Univ. of California, San Francisco, CA (United States)
  4. Univ. of Florida, Gainesville, FL (United States)
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Using a large-scale “genomic enzymology” approach, we (i) assigned novel ATP-dependent four-carbon acid sugar kinase functions to members of the DUF1537 protein family (domain of unknown function; Pfam families PF07005 and PF17042) and (ii) discovered novel catabolic pathways ford-threonate,l-threonate, andd-erythronate. The experimentally determined ligand specificities of several solute binding proteins (SBPs) for TRAP (tripartite ATP-independent permease) transporters for four-carbon acids, includingd-erythronate andl-erythronate, were used to constrain the substrates for the catabolic pathways that degrade the SBP ligands to intermediates in central carbon metabolism. Sequence similarity networks and genome neighborhood networks were used to identify the enzyme components of the pathways. Conserved genome neighborhoods encoded SBPs as well as permease components of the TRAP transporters, members of the DUF1537 family, and a member of the 4-hydroxy-l-threonine 4-phosphate dehydrogenase (PdxA) oxidative decarboxylase, class II aldolase, or ribulose 1,5-bisphosphate carboxylase/oxygenase, large subunit (RuBisCO) superfamily. Because the characterized substrates of members of the PdxA, class II aldolase, and RuBisCO superfamilies are phosphorylated, we postulated that the members of the DUF1537 family are novel ATP-dependent kinases that participate in catabolic pathways for four-carbon acid sugars. We determined that (i) the DUF1537/PdxA pair participates in a pathway for the conversion ofd-threonate to dihydroxyacetone phosphate and CO2 and (ii) the DUF1537/class II aldolase pair participates in pathways for the conversion ofd-erythronate andl-threonate (epimers at carbon-3) to dihydroxyacetone phosphate and CO2. As a result, the physiological importance of these pathways was demonstrated in vivo by phenotypic and genetic analyses.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH)
Grant/Contract Number:
AC02-06CH11357; U54GM093342
OSTI ID:
1329421
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 29; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 39 works
Citation information provided by
Web of Science

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Cited By (6)

Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis journal June 2017
How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation journal January 2020
AGeNNT: annotation of enzyme families by means of refined neighborhood networks journal May 2017
A Survey of Pyridoxal 5′-Phosphate-Dependent Proteins in the Gram-Positive Model Bacterium Bacillus subtilis journal May 2019
AGeNNT: annotation of enzyme families by means of refined neighborhood networks text January 2017
The Escherichia coli transcriptome mostly consists of independently regulated modules journal December 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DUF1537
kinase
four-carbon acid sugars
conserved
genome neighborhoods
genomic enzymology