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Title: A family of metal-dependent phosphatases implicated in metabolite damage-control

DUF89 family proteins occur widely in pro- and eukaryotes but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), subfamily II being split into standalone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metaldependent phosphatase activity against reactive phosphoesters or their damaged forms, notably sugar phosphates (subfamilies II and III), phosphopantetheine and its S-sulfonate or sulfonate (subfamily II-PanK fusions), and nucleotides (subfamily I). Genetic and comparative genomic data strongly associated DUF89 genes with phosphoester metabolism. The crystal structure of the yeast (Saccharomyces cerevisiae) subfamily III protein YMR027W revealed a novel phosphatase active site with fructose 6-phosphate and Mg 2+ bound near conserved signature residues Asp254 and Asn255 that are critical for activity. These findings indicate that DUF89 proteins are previously unrecognized hydrolases whose characteristic in vivo function is to limit potentially harmful buildups of normal or damaged phosphometabolites.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [3] ;  [3] ;  [3] ;  [3] ;  [3] ;  [1] ;  [1] ;  [1] ;  [1] ;  [5] ;  [1] ;  [4] ;  [3] ;  [3] ;  [1]
  1. Univ. of Florida, Gainesville, FL (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. Univ. of Toronto, ON (Canada)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
  5. Univ. of California, Davis, CA (United States)
Publication Date:
Report Number(s):
BNL-112717-2016-JA
Journal ID: ISSN 1552-4450
Grant/Contract Number:
SC00112704
Type:
Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 8; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1341633