Literature summary for 5.1.1.18 extracted from

Smith, M.A.; Mack, V.; Ebneth, A.; Moraes, I.; Felicetti, B.; Wood, M.; Schonfeld, D.; Mather, O.; Cesura, A.; Barker, J.
The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding (2010), J. Biol. Chem., 285, 12873-12881.

Activating Compound

Activating Compound	Comment	Organism	Structure
ATP	-	Rattus norvegicus
ATP	-	Homo sapiens

Application

Application	Comment	Organism
drug development	serine racemase is a promising target for the development of specific inhibitors in the treatment of disorders related to NMDAR dysfunction. Analysis of the molecular basis for rational drug design using the X-ray crystal structures of human and rat serine racemase	Rattus norvegicus
drug development	serine racemase is a promising target for the development of specific inhibitors in the treatment of disorders related to NMDAR dysfunction. Analysis of the molecular basis for rational drug design using the X-ray crystal structures of human and rat serine racemase	Homo sapiens
pharmacology	because D-serine affects NMDAR signaling throughout the brain, serine racemase is a promising target for the treatment of disorders related to NMDAR dysfunction	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
expression of His-tagged enzyme mutant in Escherichia coli strain Rosetta 2 (DE3)	Rattus norvegicus
expression of His-tagged enzyme mutant in Escherichia coli strain Rosetta 2 (DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant mutant C2D/C6D by sitting drop vapor diffusion, 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 100 mM NaCl, 10% glycerol, 0.05 mM PLP, 2 mM MgCl2, 5 mM dithiothreitol, mixed with 25% PEG 3350, 200 mM sodium malonate, and 50 mM MnCl2 as the reservoir solution, 4 days, the selenomethionine-labeled enzyme crystals grow under similar conditions, X-ray diffraction structure determination and analysis at 1.5-1.7 A resolution	Homo sapiens
purified recombinant mutant C2D/C6D by sitting drop vapor diffusion, 35 mg/ml protein, from 55% v/v Tacsimate, i.e. 1.8305 M malonic acid, 0.25 M ammonium citrate tribasic, 0.12 M succinic acid, 0.3 M DL-malic acid, 0.4 M sodium acetate trihydrate, 0.5 M sodium formate, and 0.16 M ammonium tartrate dibasic, pH 8.0, and 100 mM Bis-Tris propane, pH 7.8, 10 days, X-ray diffraction structure determination and analysis at 1.8-1.95 A resolution	Rattus norvegicus

Crystallization (Comment)

Organism

purified recombinant mutant C2D/C6D by sitting drop vapor diffusion, 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 100 mM NaCl, 10% glycerol, 0.05 mM PLP, 2 mM MgCl2, 5 mM dithiothreitol, mixed with 25% PEG 3350, 200 mM sodium malonate, and 50 mM MnCl2 as the reservoir solution, 4 days, the selenomethionine-labeled enzyme crystals grow under similar conditions, X-ray diffraction structure determination and analysis at 1.5-1.7 A resolution

Homo sapiens

purified recombinant mutant C2D/C6D by sitting drop vapor diffusion, 35 mg/ml protein, from 55% v/v Tacsimate, i.e. 1.8305 M malonic acid, 0.25 M ammonium citrate tribasic, 0.12 M succinic acid, 0.3 M DL-malic acid, 0.4 M sodium acetate trihydrate, 0.5 M sodium formate, and 0.16 M ammonium tartrate dibasic, pH 8.0, and 100 mM Bis-Tris propane, pH 7.8, 10 days, X-ray diffraction structure determination and analysis at 1.8-1.95 A resolution

Rattus norvegicus

Protein Variants

Protein Variants	Comment	Organism
C2D/C6D	site-directed mutagenesis	Rattus norvegicus
C2D/C6D	site-directed mutagenesis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
phosphatidylinositol-4,5-bisphosphate	-	Homo sapiens
phosphatidylinositol-4,5-bisphosphate	-	Rattus norvegicus

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	activates	Rattus norvegicus
Mg2+	activates	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-serine	Rattus norvegicus	-	D-serine	-	r
L-serine	Homo sapiens	-	D-serine	-	r

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9GZT4	-	-
Rattus norvegicus	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme mutant from Escherichia coli strain Rosetta 2 (DE3) by affinity chromatography and gel filtration to over 98% purity	Rattus norvegicus
recombinant His-tagged enzyme mutant from Escherichia coli strain Rosetta 2 (DE3) by affinity chromatography and gel filtration to over 98% purity	Homo sapiens

Reaction

Reaction	Comment	Organism	Reaction ID
L-serine = D-serine	racemase and dehydratase reaction mechanism of serine racemase, overview	Rattus norvegicus	a
L-serine = D-serine	racemase and dehydratase reaction mechanism of serine racemase, overview	Homo sapiens	a

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Rattus norvegicus	-
brain	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-serine	-	Rattus norvegicus	D-serine	-	r
L-serine	-	Homo sapiens	D-serine	-	r

Subunits

Subunits	Comment	Organism
More	the enzyme structures shows a fold typical of beta-family pyridoxal 5'-phosphate enzymes, with both a large domain and a flexible small domain associated into a symmetric dimer, and indicated a ligand-induced rearrangement of the small domain that organizes the active site for specific turnover of the substrate, ligand-induced shift of small and large domains of the racemase, structure analysis, overview	Rattus norvegicus
More	the enzyme structures shows a fold typical of beta-family pyridoxal 5'-phosphate enzymes, with both a large domain and a flexible small domain associated into a symmetric dimer, and indicated a ligand-induced rearrangement of the small domain that organizes the active site for specific turnover of the substrate, ligand-induced shift of small and large domains of the racemase, structure analysis, overview	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Rattus norvegicus
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
9	-	assay at	Rattus norvegicus
9	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
pyridoxal 5'-phosphate	dependent on, binding site structure, overview	Rattus norvegicus
pyridoxal 5'-phosphate	dependent on, binding site structure, overview	Homo sapiens