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

Lili Huang; Anna Khusnutdinova; Boguslaw Nocek; Greg Brown; Xiaohui Xu; Hong Cui; Pierre Petit; Robert Flick; Rémi Zallot; Kelly Balmant; Michael J. Ziemak; John Shanklin; Valérie De Crécy-Lagard; Oliver Fiehn; Jesse F. Gregory; Andrzej Joachimiak; Alexei Savchenko; Alexander F. Yakunin; Andrew D. Hanson

doi:10.1038/nchembio.2108

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

Lili Huang
, Anna Khusnutdinova
, Boguslaw Nocek
, Greg Brown
, Xiaohui Xu
, Hong Cui
, Pierre Petit
, Robert Flick
, Rémi Zallot
, Kelly Balmant
, Michael J. Ziemak
, John Shanklin
, Valérie De Crécy-Lagard
, Oliver Fiehn
, Jesse F. Gregory
, Andrzej Joachimiak
, Alexei Savchenko
, Alexander F. Yakunin
, Andrew D. Hanson

Biochemistry and Cell Biology

University of Florida
University of Toronto
Argonne National Laboratory
University of California at Davis

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-Alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent 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.

Original language	English
Pages (from-to)	621-627
Number of pages	7
Journal	Nature Chemical Biology
Volume	12
Issue number	8
DOIs	https://doi.org/10.1038/nchembio.2108
State	Published - Aug 1 2016

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Huang, L., Khusnutdinova, A., Nocek, B., Brown, G., Xu, X., Cui, H., Petit, P., Flick, R., Zallot, R., Balmant, K., Ziemak, M. J., Shanklin, J., De Crécy-Lagard, V., Fiehn, O., Gregory, J. F., Joachimiak, A., Savchenko, A., Yakunin, A. F., & Hanson, A. D. (2016). A family of metal-dependent phosphatases implicated in metabolite damage-control. Nature Chemical Biology, 12(8), 621-627. https://doi.org/10.1038/nchembio.2108

@article{fab4554747af4c9492c18c598267360b,

title = "A family of metal-dependent phosphatases implicated in metabolite damage-control",

abstract = "DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-Alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent 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.",

author = "Lili Huang and Anna Khusnutdinova and Boguslaw Nocek and Greg Brown and Xiaohui Xu and Hong Cui and Pierre Petit and Robert Flick and R{\'e}mi Zallot and Kelly Balmant and Ziemak, \{Michael J.\} and John Shanklin and \{De Cr{\'e}cy-Lagard\}, Val{\'e}rie and Oliver Fiehn and Gregory, \{Jesse F.\} and Andrzej Joachimiak and Alexei Savchenko and Yakunin, \{Alexander F.\} and Hanson, \{Andrew D.\}",

year = "2016",

month = aug,

day = "1",

doi = "10.1038/nchembio.2108",

language = "English",

volume = "12",

pages = "621--627",

journal = "Nature Chemical Biology",

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Huang, L, Khusnutdinova, A, Nocek, B, Brown, G, Xu, X, Cui, H, Petit, P, Flick, R, Zallot, R, Balmant, K, Ziemak, MJ, Shanklin, J, De Crécy-Lagard, V, Fiehn, O, Gregory, JF, Joachimiak, A, Savchenko, A, Yakunin, AF & Hanson, AD 2016, 'A family of metal-dependent phosphatases implicated in metabolite damage-control', Nature Chemical Biology, vol. 12, no. 8, pp. 621-627. https://doi.org/10.1038/nchembio.2108

TY - JOUR

T1 - A family of metal-dependent phosphatases implicated in metabolite damage-control

AU - Huang, Lili

AU - Khusnutdinova, Anna

AU - Nocek, Boguslaw

AU - Brown, Greg

AU - Xu, Xiaohui

AU - Cui, Hong

AU - Petit, Pierre

AU - Flick, Robert

AU - Zallot, Rémi

AU - Balmant, Kelly

AU - Ziemak, Michael J.

AU - Shanklin, John

AU - De Crécy-Lagard, Valérie

AU - Fiehn, Oliver

AU - Gregory, Jesse F.

AU - Joachimiak, Andrzej

AU - Savchenko, Alexei

AU - Yakunin, Alexander F.

AU - Hanson, Andrew D.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-Alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent 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.

AB - DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-Alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent 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.

UR - https://www.scopus.com/pages/publications/84975290954

U2 - 10.1038/nchembio.2108

DO - 10.1038/nchembio.2108

M3 - Article

C2 - 27322068

AN - SCOPUS:84975290954

SN - 1552-4450

VL - 12

SP - 621

EP - 627

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 8

ER -

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

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