Evolutionary and Structural Analyses of the Mammalian Haloacid Dehalogenase-Type Phosphatases AUM and Chronophin Provide Insight into the Basis of their Different Substrate Specificities
Mammalian haloacid dehalogenase (HAD)-type phosphatases are an emerging family of phosphatases with important functions in physiology and disease, yet little is known about the basis of their substrate specificity. Here, we characterize a previously unexplored HAD family member (gene annotation: phosphoglycolate phosphatase) that we termed AUM, for aspartate-based, ubiquitous, Mg(2+)-dependent phosphatase. AUM is a tyrosine-specific paralog of the serine/threonine-specific protein and pyridoxal 5'-phosphate-directed HAD phosphatase chronophin. Comparative evolutionary and biochemical analyses reveal that a single, differently conserved residue in the cap domain of either AUM or chronophin is crucial for phosphatase specificity. We have solved the X-ray crystal structure of the AUM cap fused to the catalytic core of chronophin to 2.65 Å resolution and present a detailed view of the catalytic clefts of AUM and chronophin that explains their substrate preferences. Our findings identify a small number of cap domain residues that encode the different substrate specificities of AUM and chronophin.
%0 Journal Article
%1 pmid24338473
%A Seifried, A.
%A Knobloch, G.
%A Duraphe, P. S.
%A Segerer, G.
%A Manhard, J.
%A Schindelin, H.
%A Schultz, J.
%A Gohla, A.
%D 2014
%J J. Biol. Chem.
%K myown protein_evolution
%N 6
%P 3416-31
%T Evolutionary and Structural Analyses of the Mammalian Haloacid Dehalogenase-Type Phosphatases AUM and Chronophin Provide Insight into the Basis of their Different Substrate Specificities
%V 289
%X Mammalian haloacid dehalogenase (HAD)-type phosphatases are an emerging family of phosphatases with important functions in physiology and disease, yet little is known about the basis of their substrate specificity. Here, we characterize a previously unexplored HAD family member (gene annotation: phosphoglycolate phosphatase) that we termed AUM, for aspartate-based, ubiquitous, Mg(2+)-dependent phosphatase. AUM is a tyrosine-specific paralog of the serine/threonine-specific protein and pyridoxal 5'-phosphate-directed HAD phosphatase chronophin. Comparative evolutionary and biochemical analyses reveal that a single, differently conserved residue in the cap domain of either AUM or chronophin is crucial for phosphatase specificity. We have solved the X-ray crystal structure of the AUM cap fused to the catalytic core of chronophin to 2.65 Å resolution and present a detailed view of the catalytic clefts of AUM and chronophin that explains their substrate preferences. Our findings identify a small number of cap domain residues that encode the different substrate specificities of AUM and chronophin.
@article{pmid24338473,
abstract = {Mammalian haloacid dehalogenase (HAD)-type phosphatases are an emerging family of phosphatases with important functions in physiology and disease, yet little is known about the basis of their substrate specificity. Here, we characterize a previously unexplored HAD family member (gene annotation: phosphoglycolate phosphatase) that we termed AUM, for aspartate-based, ubiquitous, Mg(2+)-dependent phosphatase. AUM is a tyrosine-specific paralog of the serine/threonine-specific protein and pyridoxal 5'-phosphate-directed HAD phosphatase chronophin. Comparative evolutionary and biochemical analyses reveal that a single, differently conserved residue in the cap domain of either AUM or chronophin is crucial for phosphatase specificity. We have solved the X-ray crystal structure of the AUM cap fused to the catalytic core of chronophin to 2.65 Å resolution and present a detailed view of the catalytic clefts of AUM and chronophin that explains their substrate preferences. Our findings identify a small number of cap domain residues that encode the different substrate specificities of AUM and chronophin.},
added-at = {2014-01-15T11:45:31.000+0100},
author = {Seifried, A. and Knobloch, G. and Duraphe, P. S. and Segerer, G. and Manhard, J. and Schindelin, H. and Schultz, J. and Gohla, A.},
biburl = {https://www.bibsonomy.org/bibtex/2df7634f078fec6b15b86d09fe0d2e584/jschultz},
interhash = {abb6fdc681016755c67b31b53682224d},
intrahash = {df7634f078fec6b15b86d09fe0d2e584},
journal = {J. Biol. Chem.},
keywords = {myown protein_evolution},
month = feb,
number = 6,
pages = {3416-31},
timestamp = {2017-06-09T10:18:01.000+0200},
title = {{{E}volutionary and {S}tructural {A}nalyses of the {M}ammalian {H}aloacid {D}ehalogenase-{T}ype {P}hosphatases {A}{U}{M} and {C}hronophin {P}rovide {I}nsight into the {B}asis of their {D}ifferent {S}ubstrate {S}pecificities}},
volume = 289,
year = 2014
}