Application | Comment | Organism |
---|---|---|
additional information | selective inhibition of GAPDHS, one of the glycolytic isozymes with restricted expression during spermatogenesis, is a potential strategy for the development of a non-hormonal contraceptive that directly blocks sperm function. Detailed structural comparisons of sperm-specific glyceraldehyde 3-phosphate dehydrogenase, spermatogenic (GAPDHS) and the somatic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) isozyme can facilitate the identification of selective GAPDHS inhibitors for contraceptive development | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant enzyme expression | Homo sapiens |
recombinant enzyme expression of GST-tagged GAPDH in gapA-deficient Escherichia coli strain DS112 | Mus musculus |
recombinant enzyme expression of GST-tagged tGAPDHS (amino acids 76-408) in gapA-deficient Escherichia coli strain DS112 | Homo sapiens |
recombinant enzyme expression of MBP-tagged tGAPDHS (amino acids 106-438) in gapA-deficient Escherichia coli strain DS112 | Mus musculus |
Crystallization (Comment) | Organism |
---|---|
analysis of human GAPDH crystal structure, PDB ID 1U8F | Homo sapiens |
purified recombinant apo-enzyme tGAPDHS, hanging-drop vapor-diffusion method, 10 mg/ml in 10 mM HEPES, pH 7.5, 500 mM NaCl, 5% glycerol, 0.5 mM TCEP, and 0.01% of sodium azide, is mixed in a 1:1 volume ratio with reservoir solution containing 0.2 M Na2SO4, 0.1 M Bis-Tris propane, pH 6.5, and 20% PEG 3350, 20°C, 2 days, crystallization of purified recombinant holoenzyme tGAPDHS in complex with NAD+, hanging-drop vapor-diffusion method, 10 mg/ml in 10 mM HEPES, pH 7.5, 500 mM NaCl, 5% glycerol, 0.5 mM TCEP, and 0.01% of sodium azide, is mixed in a 1:1 volume ratio with reservoir solution 0.2M NaNO3, and 20% PEG3350, 20°C, 2 days, X-ray diffraction structure determination and analysis at a.86 A (apoenzyme) and 1.73 A (holoenzyme) resolutions, method screening | Homo sapiens |
purified recombinant apo-enzyme tGAPDHS, hanging-drop vapor-diffusion method, 3 mg/ml protein in PBS is mixed in a 1:1 volume ratio with reservoir solution containing 0.2 M potassium thiocyanate, 0.1 M Bis-Tris propane, pH 6.5, and 20% PEG 3350, 20°C, 6 days, X-ray diffraction structure determination and analysis at 2.01 A resolution | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
T0501_7749 | 2-[2-amino-3-(4-methylphenyl)sulfonylpyrrolo[3,2-b]quinoxalin-1-yl]-1-(4-nitrophenyl)ethanol, a small-molecule, highly selective isozyme GAPDHS inhibitor, molecular docking simulations in GAPDHS and GAPDH isozymes, binding structure, overview; 2-[2-amino-3-(4-methylphenyl)sulfonylpyrrolo[3,2-b]quinoxalin-1-yl]-1-(4-nitrophenyl)ethanol, identification of a small-molecule GAPDHS inhibitor with micromolar potency and high selectivity that exerts the expected inhibitory effects on sperm glycolysis and motility. The compound causes significant reductions in the percentage of motile human sperm. Molecular docking simulations in GAPDHS and GAPDH isozymes, binding structure, overview | Homo sapiens | |
T0501_7749 | 2-[2-amino-3-(4-methylphenyl)sulfonylpyrrolo[3,2-b]quinoxalin-1-yl]-1-(4-nitrophenyl)ethanol, a small-molecule, highly selective isozyme GAPDHS inhibitor, molecular docking simulations in GAPDHS and GAPDH isozymes, binding structure, overview; 2-[2-amino-3-(4-methylphenyl)sulfonylpyrrolo[3,2-b]quinoxalin-1-yl]-1-(4-nitrophenyl)ethanol, a small-molecule, highly selective isozymeGAPDHS inhibitor, the compound causes significant reductions in mouse sperm lactate production and in the percentage of motile mouse sperm. Molecular docking simulations in GAPDHS and GAPDH isozymes, binding structure, overview | Mus musculus | |
T0506_9350 | 1-cyclohexyl-3-[4-[(4-methoxyphenyl)sulfamoyl]-2-nitroanilino]urea, a partial selective isozyme GAPDH inhibitor, binding structure, overview; 1-cyclohexyl-3-[4-[(4-methoxyphenyl)sulfamoyl]-2-nitroanilino]urea, a partial selective isozyme GAPDH inhibitor, binding structure, overview. T0506_9350 inhibition of human and mouse tGAPDHS is competitive with both D-glyceraldehyde 3-phosphate and NAD+ | Homo sapiens | |
T0506_9350 | 1-cyclohexyl-3-[4-[(4-methoxyphenyl)sulfamoyl]-2-nitroanilino]urea, a partial selective isozyme GAPDH inhibitor, binding structure, overview. T0506_9350 inhibition of human and mouse tGAPDHS is competitive with both D-glyceraldehyde 3-phosphate and NAD+ | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
D-glyceraldehyde 3-phosphate + phosphate + NAD+ | Homo sapiens | - |
3-phospho-D-glyceroyl phosphate + NADH + H+ | - |
? | |
D-glyceraldehyde 3-phosphate + phosphate + NAD+ | Mus musculus | - |
3-phospho-D-glyceroyl phosphate + NADH + H+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O14556 | - |
- |
Homo sapiens | P04406 | - |
- |
Mus musculus | P16858 | - |
- |
Mus musculus | Q64467 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant GST-tagged GAPDH from gapA-deficient Escherichia coli strain DS112 by glutathione affinity chromatography, and on-column cleavage of the GST-tag by bovine thrombin before elution of the enzyme | Mus musculus |
recombinant GST-tagged tGAPDHS from gapA-deficient Escherichia coli strain DS112 by glutathione affinity chromatography, and on-column cleavage of the GST-tag by bovine thrombin before elution of the enzyme | Homo sapiens |
recombinant MBP-tagged tGAPDHS from gapA-deficient Escherichia coli strain DS112 by amylose affinity chromatography, followed by cleavage of the MBP-tag by bovine thrombin dialysis, and anion exchange chromatography | Mus musculus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
commercial preparation | purified from erythrocytes | Homo sapiens | - |
sperm cell | sperm-specific glyceraldehyde 3-phosphate dehydrogenase, restricted enzyme expression during spermatogenesis | Homo sapiens | - |
sperm cell | sperm-specific glyceraldehyde 3-phosphate dehydrogenase, restricted enzyme expression during spermatogenesis | Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
D-glyceraldehyde 3-phosphate + phosphate + NAD+ | - |
Homo sapiens | 3-phospho-D-glyceroyl phosphate + NADH + H+ | - |
? | |
D-glyceraldehyde 3-phosphate + phosphate + NAD+ | - |
Mus musculus | 3-phospho-D-glyceroyl phosphate + NADH + H+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
GAPDH | - |
Homo sapiens |
GAPDH | - |
Mus musculus |
GAPDHS | - |
Homo sapiens |
GAPDHS | - |
Mus musculus |
glyceraldehyde 3-phosphate dehydrogenase | - |
Homo sapiens |
glyceraldehyde 3-phosphate dehydrogenase | - |
Mus musculus |
glyceraldehyde 3-phosphate dehydrogenase-S | - |
Homo sapiens |
glyceraldehyde 3-phosphate dehydrogenase-S | - |
Mus musculus |
somatic glyceraldehyde 3-phosphate dehydrogenase | - |
Homo sapiens |
somatic glyceraldehyde 3-phosphate dehydrogenase | - |
Mus musculus |
sperm-specific glyceraldehyde 3-phosphate dehydrogenase | - |
Homo sapiens |
sperm-specific glyceraldehyde 3-phosphate dehydrogenase | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens | |
NAD+ | - |
Mus musculus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | inhibition kinetics | Homo sapiens | |
additional information | - |
additional information | inhibition kinetics | Mus musculus | |
0.0569 | - |
T0506_9350 | versus NAD+, pH and temperature not specified in the publication | Mus musculus | |
0.0602 | - |
T0506_9350 | versus NAD+, pH and temperature not specified in the publication | Homo sapiens | |
0.0633 | - |
T0506_9350 | versus D-glyceraldehyde 3-phosphate, pH and temperature not specified in the publication | Homo sapiens | |
0.071 | - |
T0506_9350 | versus D-glyceraldehyde 3-phosphate, pH and temperature not specified in the publication | Mus musculus |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0012 | - |
pH and temperature not specified in the publication | Homo sapiens | T0501_7749 | |
0.0385 | - |
pH and temperature not specified in the publication | Homo sapiens | T0501_7749 | |
0.0958 | - |
pH and temperature not specified in the publication | Homo sapiens | T0506_9350 | |
0.86 | - |
pH and temperature not specified in the publication | Homo sapiens | T0506_9350 |
General Information | Comment | Organism |
---|---|---|
malfunction | GAPDHS inhibitor effects on sperm motility and metabolism, overview | Homo sapiens |
malfunction | GAPDHS inhibitor effects on sperm motility and metabolism, overview | Mus musculus |
additional information | detailed structural comparisons of sperm-specific glyceraldehyde 3-phosphate dehydrogenase, spermatogenic (GAPDHS) and the somatic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) isozyme of mouse and human, homology modeling of human and mouse GAPDH and GAPDHS isozymes, and binding sites for GAP and NAD+, determined by reference to structures PDB 1DC4 and 1DC6 and crystal structure of Palinurus versicolor GAPDH, PDB ID 1CRW, overview | Homo sapiens |
additional information | detailed structural comparisons of sperm-specific glyceraldehyde 3-phosphate dehydrogenase, spermatogenic (GAPDHS) and the somatic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) isozyme of mouse and human, homology modeling of human and mouse GAPDH and GAPDHS isozymes, and binding sites for GAP and NAD+, determined by reference to structures PDB 1DC4 and 1DC6 and crystal structure of Palinurus versicolor GAPDH, PDB ID 1CRW, overview | Mus musculus |