Dataset Information

Molecular Identification of d-Ribulokinase in Budding Yeast and Mammals.

ABSTRACT: Proteomes of even well characterized organisms still contain a high percentage of proteins with unknown or uncertain molecular and/or biological function. A significant fraction of those proteins is predicted to have catalytic properties. Here we aimed at identifying the function of the Saccharomyces cerevisiae Ydr109c protein and its human homolog FGGY, both of which belong to the broadly conserved FGGY family of carbohydrate kinases. Functionally identified members of this family phosphorylate 3- to 7-carbon sugars or sugar derivatives, but the endogenous substrate of S. cerevisiae Ydr109c and human FGGY has remained unknown. Untargeted metabolomics analysis of an S. cerevisiae deletion mutant of YDR109C revealed ribulose as one of the metabolites with the most significantly changed intracellular concentration as compared with a wild-type strain. In human HEK293 cells, ribulose could only be detected when ribitol was added to the cultivation medium, and under this condition, FGGY silencing led to ribulose accumulation. Biochemical characterization of the recombinant purified Ydr109c and FGGY proteins showed a clear substrate preference of both kinases for d-ribulose over a range of other sugars and sugar derivatives tested, including l-ribulose. Detailed sequence and structural analyses of Ydr109c and FGGY as well as homologs thereof furthermore allowed the definition of a 5-residue d-ribulokinase signature motif (TCSLV). The physiological role of the herein identified eukaryotic d-ribulokinase remains unclear, but we speculate that S. cerevisiae Ydr109c and human FGGY could act as metabolite repair enzymes, serving to re-phosphorylate free d-ribulose generated by promiscuous phosphatases from d-ribulose 5-phosphate. In human cells, FGGY can additionally participate in ribitol metabolism.

SUBMITTER: Singh C

PROVIDER: S-EPMC5247636 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Molecular Identification of d-Ribulokinase in Budding Yeast and Mammals.

Singh Charandeep C Glaab Enrico E Linster Carole L CL

The Journal of biological chemistry 20161201 3

Proteomes of even well characterized organisms still contain a high percentage of proteins with unknown or uncertain molecular and/or biological function. A significant fraction of those proteins is predicted to have catalytic properties. Here we aimed at identifying the function of the Saccharomyces cerevisiae Ydr109c protein and its human homolog FGGY, both of which belong to the broadly conserved FGGY family of carbohydrate kinases. Functionally identified members of this family phosphorylate ...[more]

PMID: 27909055

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Project description:The specification and maintenance of cell fates is essential to the development of multicellular organisms. However, the precise molecular mechanisms in cell fate selection are, to our knowledge, poorly understood due to the complexity of multiple interconnected pathways. In this study, model-based quantitative analysis is used to explore how to maintain distinguished cell fates between cell-cycle commitment and mating arrest in budding yeast. We develop a full mathematical model of an interlinked regulatory network based on the available experimental data. By theoretically defining the Start transition point, the model is able to reproduce many experimental observations of the dynamical behaviors in wild-type cells as well as in Ste5-8A and Far1-S87A mutants. Furthermore, we demonstrate that a moderate ratio between Cln1/2?Far1 inhibition and Cln1/2?Ste5 inhibition is required to ensure a successful switch between different cell fates. We also show that the different ratios of the mutual Cln1/2 and Far1 inhibition determine the different cell fates. In addition, based on a new, definition of network entropy, we find that the Start point in wild-type cells coincides with the system's point of maximum entropy. This result indicates that Start is a transition point in the network entropy. Therefore, we theoretically explain the Start point from a network dynamics standpoint. Moreover, we analyze the biological bistablity of our model through bifurcation analysis. We find that the Cln1/2 and Cln3 production rates and the nonlinearity of SBF regulation on Cln1/2 production are potential determinants for irreversible entry into a new cell fate. Finally, the quantitative computations further reveal that high specificity and fidelity of the cell-cycle and mating pathways can guarantee specific cell-fate selection. These findings show that quantitative analysis and simulations with a mathematical model are useful tools for understanding the molecular mechanisms in cell-fate decisions.

Dataset Information

Molecular Identification of d-Ribulokinase in Budding Yeast and Mammals.

Publications

Molecular Identification of d-Ribulokinase in Budding Yeast and Mammals.

Similar Datasets

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