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

Zhang, Xinshuai; Carter, Michael S.; Vetting, Matthew W.; San Francisco, Brian; Zhao, Suwen; Al-Obaidi, Nawar F.; Solbiati, Jose O.; Thiaville, Jennifer J.; de Crécy-Lagard, Valérie; Jacobson, Matthew P.; Almo, Steven C.; Gerlt, John A.

doi:10.1073/pnas.1605546113

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

Journal Article · Mon Jul 11 04:00:00 UTC 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.1605546113 · OSTI ID:1329421

Zhang, Xinshuai ^[1]; Carter, Michael S. ^[1]; Vetting, Matthew W. ^[2]; San Francisco, Brian ^[1]; Zhao, Suwen ^[3]; Al-Obaidi, Nawar F. ^[2]; Solbiati, Jose O. ^[1]; Thiaville, Jennifer J. ^[4]; de Crécy-Lagard, Valérie ^[4]; Jacobson, Matthew P. ^[3]; Almo, Steven C. ^[2]; Gerlt, John A. ^[1]

Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)
Albert Einstein College of Medicine, Bronx, NY (United States)
Univ. of California, San Francisco, CA (United States)
Univ. of Florida, Gainesville, FL (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division; NIH

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1329421

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 29 Vol. 113; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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

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

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Cited By (7)

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