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Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties.

Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P - Front Plant Sci (2013)

Bottom Line: A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation.Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells.The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Plant Redox Biology, Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

No MeSH data available.


Related in: MedlinePlus

The catalytic sites of rice cytoplasmic GAPDH and non-phosphorylating GAPDH from Streptococcus mutants.(A) Magnified representation of OsGAPC catalytic site (PDB code 3E5R). Important catalytic residues, the cofactor NAD+ and residue Cys-158 are shown as ball-and-sticks. The distances of the sulfur atom (SG) of catalytic Cys-154 from the basic residue His-181 (atom NE2), the sulfur atom of Cys-158 and the cofactor (atom C4N) are indicated by dashed lines. (B) Catalytic site representation of Streptococcus mutans non-phosphorylating GAPDH (SmGAPN; PDB code 2EUH). The catalytic residues Cys-302 and Glu-268, and the cofactor NADP+ are in ball-and-sticks representation.
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Figure 3: The catalytic sites of rice cytoplasmic GAPDH and non-phosphorylating GAPDH from Streptococcus mutants.(A) Magnified representation of OsGAPC catalytic site (PDB code 3E5R). Important catalytic residues, the cofactor NAD+ and residue Cys-158 are shown as ball-and-sticks. The distances of the sulfur atom (SG) of catalytic Cys-154 from the basic residue His-181 (atom NE2), the sulfur atom of Cys-158 and the cofactor (atom C4N) are indicated by dashed lines. (B) Catalytic site representation of Streptococcus mutans non-phosphorylating GAPDH (SmGAPN; PDB code 2EUH). The catalytic residues Cys-302 and Glu-268, and the cofactor NADP+ are in ball-and-sticks representation.

Mentions: The structure of the active site of cytoplasmic OsGAPDH is very similar to that of other glycolytic and also chloroplastic GAPDHs. Sequence alignments show a highly conserved region between residues 150 and 161 (Figure 2), corresponding to the substrate binding site. The two most important catalytic residues are Cys-154 (corresponding to Cys-149 in H. americanus and B. stearothermophilus GAPDHs, the first solved GAPDH structures, Table 1) and His-181 (corresponding to His-176 in H. americanus and B. stearothermophilus GAPDHs; Figure 2). The side-chain of Cys-154 points toward His-181 and the distance between the sulfur atom of the first residue and the closest nitrogen atom (NE2) of the second residue is 4.03 Å on average (Figure 3A). The minimum distance of Cys-154 from the coenzyme nicotinamide ring is 3.69 Å (Figure 3A).


Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties.

Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P - Front Plant Sci (2013)

The catalytic sites of rice cytoplasmic GAPDH and non-phosphorylating GAPDH from Streptococcus mutants.(A) Magnified representation of OsGAPC catalytic site (PDB code 3E5R). Important catalytic residues, the cofactor NAD+ and residue Cys-158 are shown as ball-and-sticks. The distances of the sulfur atom (SG) of catalytic Cys-154 from the basic residue His-181 (atom NE2), the sulfur atom of Cys-158 and the cofactor (atom C4N) are indicated by dashed lines. (B) Catalytic site representation of Streptococcus mutans non-phosphorylating GAPDH (SmGAPN; PDB code 2EUH). The catalytic residues Cys-302 and Glu-268, and the cofactor NADP+ are in ball-and-sticks representation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824636&req=5

Figure 3: The catalytic sites of rice cytoplasmic GAPDH and non-phosphorylating GAPDH from Streptococcus mutants.(A) Magnified representation of OsGAPC catalytic site (PDB code 3E5R). Important catalytic residues, the cofactor NAD+ and residue Cys-158 are shown as ball-and-sticks. The distances of the sulfur atom (SG) of catalytic Cys-154 from the basic residue His-181 (atom NE2), the sulfur atom of Cys-158 and the cofactor (atom C4N) are indicated by dashed lines. (B) Catalytic site representation of Streptococcus mutans non-phosphorylating GAPDH (SmGAPN; PDB code 2EUH). The catalytic residues Cys-302 and Glu-268, and the cofactor NADP+ are in ball-and-sticks representation.
Mentions: The structure of the active site of cytoplasmic OsGAPDH is very similar to that of other glycolytic and also chloroplastic GAPDHs. Sequence alignments show a highly conserved region between residues 150 and 161 (Figure 2), corresponding to the substrate binding site. The two most important catalytic residues are Cys-154 (corresponding to Cys-149 in H. americanus and B. stearothermophilus GAPDHs, the first solved GAPDH structures, Table 1) and His-181 (corresponding to His-176 in H. americanus and B. stearothermophilus GAPDHs; Figure 2). The side-chain of Cys-154 points toward His-181 and the distance between the sulfur atom of the first residue and the closest nitrogen atom (NE2) of the second residue is 4.03 Å on average (Figure 3A). The minimum distance of Cys-154 from the coenzyme nicotinamide ring is 3.69 Å (Figure 3A).

Bottom Line: A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation.Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells.The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Plant Redox Biology, Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

No MeSH data available.


Related in: MedlinePlus