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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jin, Ke Koonin, Eugene V. Tan, Kemin Flick, Robert Babu, Mohan Savchenko, Alexei Joachimiak, Andrzej De Crécy-lagard, Valérie Yakunin, Alexander F. Wolf, Yuri I. Khusnutdinova, Anna Evdokimova, Elena Edwards, Aled M. Nocek, Boguslaw Hasnain, Ghulam Hanson, Andrew D. Kuznetsova, Ekaterina Brown, Greg Makarova, Kira S. Zallot, Rémi |
| Description | Author Affiliation: Kuznetsova E ( From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.); Nocek B ( the Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.); Brown G ( the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.); Makarova KS ( the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894.); Flick R ( the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.); Wolf YI ( the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894.); Khusnutdinova A ( the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.); Evdokimova E ( the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.); Jin K ( the Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan S4S 0A2, Canada, and.); Tan K ( the Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.); Hanson AD ( the Horticultural Sciences Department, Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611.); Hasnain G ( the Horticultural Sciences Department, Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611.); Zallot R ( the Horticultural Sciences Department, Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611.); de Crécy-Lagard V ( the Horticultural Sciences Department, Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611.); Babu M ( the Department of Biochemistry, Research and Innovation Centre, University of Regina, Regina, Saskatchewan S4S 0A2, Canada, and.); Savchenko A ( the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.); Joachimiak A ( the Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.); Edwards AM ( From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada, the Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.); Koonin EV ( the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894.); Yakunin AF ( the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada, a.iakounine@utoronto.ca.) |
| Abstract | The haloacid dehalogenase (HAD)-like enzymes comprise a large superfamily of phosphohydrolases present in all organisms. The Saccharomyces cerevisiae genome encodes at least 19 soluble HADs, including 10 uncharacterized proteins. Here, we biochemically characterized 13 yeast phosphatases from the HAD superfamily, which includes both specific and promiscuous enzymes active against various phosphorylated metabolites and peptides with several HADs implicated in detoxification of phosphorylated compounds and pseudouridine. The crystal structures of four yeast HADs provided insight into their active sites, whereas the structure of the YKR070W dimer in complex with substrate revealed a composite substrate-binding site. Although the S. cerevisiae and Escherichia coli HADs share low sequence similarities, the comparison of their substrate profiles revealed seven phosphatases with common preferred substrates. The cluster of secondary substrates supporting significant activity of both S. cerevisiae and E. coli HADs includes 28 common metabolites that appear to represent the pool of potential activities for the evolution of novel HAD phosphatases. Evolution of novel substrate specificities of HAD phosphatases shows no strict correlation with sequence divergence. Thus, evolution of the HAD superfamily combines the conservation of the overall substrate pool and the substrate profiles of some enzymes with remarkable biochemical and structural flexibility of other superfamily members. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 30 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-07-24 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Evolution, Molecular Hydrolases Chemistry Metabolism Saccharomyces Cerevisiae Enzymology Amino Acid Sequence Genetics Binding Sites Catalysis Catalytic Domain Crystallography, X-Ray Genome, Fungal Kinetics Phylogeny Protein Structure, Tertiary Sequence Alignment Substrate Specificity Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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