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Literature summary extracted from

  • Miao, Y.; Tenor, J.L.; Toffaletti, D.L.; Washington, E.J.; Liu, J.; Shadrick, W.R.; Schumacher, M.A.; Lee, R.E.; Perfect, J.R.; Brennan, R.G.
    Structures of trehalose-6-phosphate phosphatase from pathogenic fungi reveal the mechanisms of substrate recognition and catalysis (2016), Proc. Natl. Acad. Sci. USA, 113, 7148-7153 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.1.3.12 purified isolated N-terminal domain of Tps2 (Tps2NTD, residues 1-534), X-ray diffraction structure determination and analysis at 2.56 A resolution, molecular replacement using the structure of Escherichia coli OtsA, a Tps1 homologue, PDB ID code 1UQU, as a search model. Purified recombinant Tps2 C-terminal trehalose-6-phosphate phosphatase domain (Tps2PD) bound to BeF3 and trehalose (Tps2PD-BeF3-trehalose transition-state complex), X-ray diffraction structure determination and analysis at 2.0 A resolution Candida albicans
3.1.3.12 purified recombinant catalytically dead Tps2PD(D24N) from Cryptococcus neoformans bound to trehalose-6-phosphate, X-ray diffraction structure determination and analysis at 2.56 A resolution Cryptococcus neoformans var. grubii H99

Protein Variants

EC Number Protein Variants Comment Organism
3.1.3.12 D24N site-directed mutagenesis, inactive mutant Candida albicans
3.1.3.12 D24N site-directed mutagenesis, inactive mutant Cryptococcus neoformans var. grubii H99
3.1.3.12 D705N site-directed mutagenesis, inactive mutant, the mutant fails to restore growth at elevated temperatures Cryptococcus neoformans var. grubii H99
3.1.3.12 additional information construction of deletion mutants deleting either the N-terminal domain or the other part of the enzyme, structure and phenotypes, overview Candida albicans
3.1.3.12 additional information deletion of the N-terminal domain of Tps2, mutant Tps2NTD, resulting in a temperature-sensitive phenotype at 39°C, structure analysis of mutant Tps2NTD Cryptococcus neoformans var. grubii H99

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.3.12 alpha,alpha-trehalose 6-phosphate + H2O Candida albicans
-
 alpha,alpha-trehalose + phosphate
-
 ?
3.1.3.12 alpha,alpha-trehalose 6-phosphate + H2O Cryptococcus neoformans var. grubii H99
-
 alpha,alpha-trehalose + phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.1.3.12 Candida albicans G1UAE0
-
-
3.1.3.12 Cryptococcus neoformans var. grubii H99 Q059G6 Filobasidiella neoformans var. grubii
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.3.12 alpha,alpha-trehalose 6-phosphate + H2O
-
 Candida albicans alpha,alpha-trehalose + phosphate
-
 ?
3.1.3.12 alpha,alpha-trehalose 6-phosphate + H2O
-
 Cryptococcus neoformans var. grubii H99 alpha,alpha-trehalose + phosphate
-
 ?
3.1.3.12 additional information analysis of mechanisms of substrate recognition and catalysis, substrate binding structure, overview Candida albicans ?
-
 ?
3.1.3.12 additional information analysis of mechanisms of substrate recognition and catalysis. Tps2 C-terminal trehalose-6-phosphate phosphatase domain (Tps2PD) undergoes a large conformational change upon substrate binding, substrate specificity of Tps2PD, oerview Cryptococcus neoformans var. grubii H99 ?
-
 ?

Subunits

EC Number Subunits Comment Organism
3.1.3.12 More Candida albicans Tps2 is an 888 amino acid residue protein that can be divided into two structural domains. The N-terminal domain (Tps2NTD) is 534 amino acid residues. The C-terminal domain of Tps2 protein (Tps2PD) encompasses amino acid residues 535 through 888 and contains the putative phosphatase domain Candida albicans

Synonyms

EC Number Synonyms Comment Organism
3.1.3.12 TPS2
-
 Candida albicans
3.1.3.12 TPS2
-
 Cryptococcus neoformans var. grubii H99
3.1.3.12 trehalose-6-phosphate phosphatase
-
 Candida albicans
3.1.3.12 trehalose-6-phosphate phosphatase
-
 Cryptococcus neoformans var. grubii H99

General Information

EC Number General Information Comment Organism
3.1.3.12 evolution Tps2PD is a member of the haloacid dehydrogenase superfamily (HADSF) phosphatases, enzymes that recognize a broad spectrum of substrates Candida albicans
3.1.3.12 malfunction a Tps2-specific inhibitor is predicted to eliminate Cryptococcus neoformans infections. Despite the lack of a trehalose biosynthesis function of the Tps2 N-terminal domain (Tps2NTD), deletion of this domain in Cryptococcus neoformans results in a temperature-sensitive phenotype at 39°C, suggesting Tps2NTD is functionally essential for cell survival at elevated temperature. Disruption of any of the direct substrate-protein residue interactions leads to significant or complete loss of phosphatase activity. The Tps2NTD closely resembles the structure of Tps1 but lacks any catalytic activity Cryptococcus neoformans var. grubii H99
3.1.3.12 malfunction disruption of any of the direct substrate-protein residue interactions leads to significant or complete loss of phosphatase activity. Mutants tps2DELTA, tps2NTDDELTA, and tps2D705N strains are unable to grow at elevated temperatures Candida albicans
3.1.3.12 metabolism the enzyme participates in the trehalose biosynthesis. Trehalose is synthesized by the conversion of glucose-6-phosphate and UDP-glucose to trehalose-6-phosphate (T6P) by Tps1 followed by dephosphorylation of T6P by Tps2 Candida albicans
3.1.3.12 metabolism the enzyme participates in the trehalose biosynthesis. Trehalose is synthesized by the conversion of glucose-6-phosphate and UDP-glucose to trehalose-6-phosphate (T6P) by Tps1 followed by dephosphorylation of T6P by Tps2 Cryptococcus neoformans var. grubii H99
3.1.3.12 additional information Candida albicans trehalose-6-phosphate phosphatase (Tps2) is one component of the trehalose biosynthetic complex, which also consists of trehalose synthase (Tps1) and the trehalose synthase regulatory protein (Tps3). Analysis of structures of the N-terminal domain of Tps2 (Tps2NTD) from Candida albicans, and a transition-state complex of the Tps2 C-terminal trehalose-6-phosphate phosphatase domain (Tps2PD) bound to BeF3 and trehalose. The Tps2PD-BeF3-trehalose complex structure reveals a closed conformation that is effected by extensive interactions between each trehalose hydroxyl group and residues of the cap and core domains of the protein, thereby providing exquisite substrate specificity. The Tps2PD-BeF3-trehalose complex structure captures an aspartyl-BeF3 covalent adduct, which closely mimics the proposed aspartyl-phosphate intermediate of the phosphatase catalytic cycle. Structures of substrate-free Tps2PD reveal an open conformation whereby the cap and core domains separate and visualize the striking conformational changes effected by substrate binding and product release and the role of two hinge regions centered at approximately residues 102-103 and 184-188. Substrate binding pocket structure and mechanism analysis, detailed overview Candida albicans
3.1.3.12 additional information structure analysis of catalytically dead Tps2PD(D24N) from Cryptococcus neoformans bound to trehalose-6-phosphate. The Tps2PD(D24N)-T6P complex structures reveals a closed conformation that is effected by extensive interactions between each trehalose hydroxyl group and residues of the cap and core domains of the protein, thereby providing exquisite substrate specificity Cryptococcus neoformans var. grubii H99