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Literature summary for 3.4.21.77 extracted from
- Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer (2010), Biol. Chem., 391, 333-343.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | PSA is produced at high levels by both androgen-dependent and -independent prostate cancers | Homo sapiens |
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | development of PSA selective inhibitors as useful tools for the targeted treatment and imaging of prostate cancer | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (4-[[([(2S,3S)-3-benzyl-1-[(3-carboxyphenyl)acetyl]-4-oxoazetidin-2-yl]carbonyl)oxy]methyl]phenyl)methanaminium trifluoroacetate | - |
Homo sapiens |  |
| 4-[([[(2S,3S)-3-benzyl-1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-4-oxoazetidin-2-yl]carbonyl]oxy)methyl]benzoic acid | - |
Homo sapiens | |
| 4-[([[(2S,3S)-3-benzyl-4-oxo-1-(phenylacetyl)azetidin-2-yl]carbonyl]oxy)methyl]benzoic acid | - |
Homo sapiens | |
| 4-[[(3-[2-[(2S,3S)-3-benzyl-2-[[(4-carboxybenzyl)oxy]carbonyl]-4-oxoazetidin-1-yl]-2-oxoethyl]benzoyl)oxy]methyl]benzoic acid | - |
Homo sapiens | |
| benzyl (2S,3S)-1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-3-(4-hydroxybenzyl)-4-oxoazetidine-2-carboxylate | - |
Homo sapiens | |
| benzyl (2S,3S)-3-benzyl-1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-4-oxoazetidine-2-carboxylate | - |
Homo sapiens | |
| benzyl 1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-3-(4-hydroxybenzyl)-4-oxoazetidine-2-carboxylate | - |
Homo sapiens | |
| additional information | beta-lactams inhibit PSA in a time-dependent manner with a 1:1 stoichiometry, competing with substrate, until a majority of PSA is converted into an irreversible inactive state. A stable covalent complex is formed between the beta-lactam and the active site serine residue in PSA. Azapeptides can inhibit PSA effectively. Benzoxazinone compounds are non-competitive inhibitors and triazoles are competitive inhibitors of PSA | Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(1S)-2-oxo-1-phenylethyl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(acetylamino)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(benzoylamino)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(formylamino)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-oxo-3-(propanoylamino)propan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-oxohexan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-[(2-methylpropanoyl)amino]-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-3-methyl-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-(dimethylamino)-1,4-dioxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-(methylsulfanyl)-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-(methylsulfinyl)-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-cyano-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-methyl-1-oxopentan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-5-(dimethylamino)-1,5-dioxopentan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-5-amino-1,5-dioxopentan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| Z-Gln-Leu-B(OH)2 | - |
Homo sapiens | |
| Z-Gln-Nle-H | - |
Homo sapiens | |
| Z-KL-H | - |
Homo sapiens | |
| Z-KLL-H | - |
Homo sapiens | |
| Z-Lys-Leu-B(OH)2 | - |
Homo sapiens | |
| Z-Lys-Leu-Leu-B(OH)2 | - |
Homo sapiens | |
| Z-Lys-Leu-Nle-B(OH)2 | - |
Homo sapiens | |
| Z-Lys-Leu-Nle-H | - |
Homo sapiens | |
| Z-Lys-Nle-H | - |
Homo sapiens | |
| Z-QL-H | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Leu-B(OH)2 | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Leu-D-Leu-H | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Leu-D-Nle-H | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Leu-Leu-B(OH)2 | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Leu-Nle-B(OH)2 | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Leu-Nle-H | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Nle-B(OH)2 | - |
Homo sapiens | |
| Z-Ser-Ser-Lys-Nle-H | - |
Homo sapiens | |
| Z-SKLL-H | - |
Homo sapiens | |
| Z-SSKAL-H | - |
Homo sapiens | |
| Z-SSKF(4-Br)L-H | - |
Homo sapiens | |
| Z-SSKFL-H | - |
Homo sapiens | |
| Z-SSKIL-H | - |
Homo sapiens | |
| Z-SSKKL-H | - |
Homo sapiens | |
| Z-SSKL-H | - |
Homo sapiens | |
| Z-SSKLD-H | - |
Homo sapiens | |
| Z-SSKLL-H | - |
Homo sapiens | |
| Z-SSKML-H | - |
Homo sapiens | |
| Z-SSKQL-H | - |
Homo sapiens | |
| Z-SSKTL-H | - |
Homo sapiens | |
| Z-SSKVL-H | - |
Homo sapiens | |
| Z-SSKYL-H | - |
Homo sapiens | |
| Z-YL-H | - |
Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.077 | - |
Mca-QFYSSNK(epsilon-dinitrophenyl) | - |
Homo sapiens | |
| 0.47 | - |
HSSKLQ-7-amido-4-methylcoumarin | - |
Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
- |
Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| prostate cancer cell | like normal prostate secretory-luminal epithelial cells, produces very high levels of PSA. High levels of active PSA in the milieu surrounding osseous and soft tissue metastases | Homo sapiens | - |
| prostate epithelium cell line | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| EHSSKLQ-7-amido-4-methylcoumarin + H2O | - |
Homo sapiens | EHSSKLQ + 7-amino-4-methylcoumarin | - |
? | |
| Fibronectin + H2O | - |
Homo sapiens | ? | - |
? | |
| HSSKLQ-7-amido-4-methylcoumarin + H2O | - |
Homo sapiens | HSSKLQ + 7-amino-4-methylcoumarin | - |
? | |
| insulin-like growth factor binding protein-3 + H2O | - |
Homo sapiens | insulin-like growth factor-1 | - |
? | |
| Laminin + H2O | - |
Homo sapiens | ? | - |
? | |
| Mca-QFYSSNK(epsilon-dinitrophenyl) + H2O | - |
Homo sapiens | ? | - |
? | |
| additional information | substrates containing tyrosine in the P1 position are hydrolyzed efficiently by PSA. Substrates with glutamine in the P1 position are less efficiently hydrolyzed, but demonstrate better specificity for PSA. The region spanning the S1 pocket contains several highly conserved residues that are critical for the structural integrity of the pocket and indirectly responsible for the maintenance of enzymatic activity. Residues such as Cys191, Cys220, Pro225, and Ser214 form crucial elements of the architecture surrounding the S1 pocket | Homo sapiens | ? | - |
? | |
| PTHrP + H2O | - |
Mus musculus | ? | - |
? | |
| PTHrP + H2O | - |
Homo sapiens | ? | - |
? | |
| semenogelin I + H2O | - |
Homo sapiens | semenogelin fragments | - |
? | |
| semenogelin II + H2O | - |
Homo sapiens | semenogelin fragments | - |
? | |
| TGFbeta2 + H2O | - |
Homo sapiens | activated TGFbeta2 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| kallikrein-related peptidase 3 | - |
Mus musculus |
| kallikrein-related peptidase 3 | - |
Homo sapiens |
| KLK3 | - |
Mus musculus |
| KLK3 | - |
Homo sapiens |
| prostate-specific antigen | - |
Mus musculus |
| prostate-specific antigen | - |
Homo sapiens |
| PSA | - |
Mus musculus |
| PSA | - |
Homo sapiens |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.000065 | - |
Z-Ser-Ser-Lys-Leu-Leu-B(OH)2 | - |
Homo sapiens | |
| 0.000226 | - |
benzyl (2S,3S)-1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-3-(4-hydroxybenzyl)-4-oxoazetidine-2-carboxylate | - |
Homo sapiens | |
| 0.000348 | - |
benzyl 1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-3-(4-hydroxybenzyl)-4-oxoazetidine-2-carboxylate | - |
Homo sapiens | |
| 0.00037 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.000398 | - |
Z-Ser-Ser-Lys-Leu-Nle-B(OH)2 | - |
Homo sapiens | |
| 0.00057 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.000918 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(formylamino)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00134 | - |
(4-[[([(2S,3S)-3-benzyl-1-[(3-carboxyphenyl)acetyl]-4-oxoazetidin-2-yl]carbonyl)oxy]methyl]phenyl)methanaminium trifluoroacetate | - |
Homo sapiens | |
| 0.00143 | - |
benzyl (2S,3S)-3-benzyl-1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-4-oxoazetidine-2-carboxylate | - |
Homo sapiens | |
| 0.00253 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-5-(dimethylamino)-1,5-dioxopentan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00384 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-(methylsulfanyl)-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00391 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(acetylamino)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00584 | - |
4-[[(3-[2-[(2S,3S)-3-benzyl-2-[[(4-carboxybenzyl)oxy]carbonyl]-4-oxoazetidin-1-yl]-2-oxoethyl]benzoyl)oxy]methyl]benzoic acid | - |
Homo sapiens | |
| 0.00598 | - |
Z-Lys-Leu-Leu-B(OH)2 | - |
Homo sapiens | |
| 0.0065 | - |
Z-SSKLL-H | - |
Homo sapiens | |
| 0.00651 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-methyl-1-oxopentan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00725 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-(methylsulfinyl)-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00814 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-cyano-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.00898 | - |
4-[([[(2S,3S)-3-benzyl-1-([3-[(benzyloxy)carbonyl]phenyl]acetyl)-4-oxoazetidin-2-yl]carbonyl]oxy)methyl]benzoic acid | - |
Homo sapiens | |
| 0.00984 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-oxo-3-(propanoylamino)propan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.01124 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-oxohexan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.01124 | - |
Z-Ser-Ser-Lys-Leu-Nle-H | - |
Homo sapiens | |
| 0.0119 | - |
Z-SSKFL-H | - |
Homo sapiens | |
| 0.01309 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-4-(dimethylamino)-1,4-dioxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.01328 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-[(2-methylpropanoyl)amino]-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.0137 | - |
Z-SSKML-H | - |
Homo sapiens | |
| 0.0139 | - |
Z-SSKYL-H | - |
Homo sapiens | |
| 0.01849 | - |
Z-Ser-Ser-Lys-Leu-B(OH)2 | - |
Homo sapiens | |
| 0.02179 | - |
Z-SSKQL-H | - |
Homo sapiens | |
| 0.02357 | - |
Z-Lys-Leu-Nle-B(OH)2 | - |
Homo sapiens | |
| 0.0243 | - |
4-[([[(2S,3S)-3-benzyl-4-oxo-1-(phenylacetyl)azetidin-2-yl]carbonyl]oxy)methyl]benzoic acid | - |
Homo sapiens | |
| 0.025 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-1-(benzoylamino)-3-oxopropan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.03421 | - |
Z-Ser-Ser-Lys-Nle-B(OH)2 | - |
Homo sapiens | |
| 0.03743 | - |
Z-SSKIL-H | - |
Homo sapiens | |
| 0.04243 | - |
Z-SKLL-H | - |
Homo sapiens | |
| 0.04521 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-5-amino-1,5-dioxopentan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.05785 | - |
Z-SSKKL-H | - |
Homo sapiens | |
| 0.07071 | - |
Z-SSKVL-H | - |
Homo sapiens | |
| 0.1 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(2S)-3-methyl-1-oxobutan-2-yl]-L-leucinamide | - |
Homo sapiens | |
| 0.1 | - |
N-[(benzyloxy)carbonyl]-L-seryl-L-seryl-L-lysyl-N-[(1S)-2-oxo-1-phenylethyl]-L-leucinamide | - |
Homo sapiens | |
| 0.1 | - |
Z-SSKTL-H | - |
Homo sapiens | |
| 0.1 | - |
Z-SSKAL-H | - |
Homo sapiens | |
| 0.1 | - |
Z-KLL-H | - |
Homo sapiens | |
| 0.2652 | - |
Z-Gln-Leu-B(OH)2 | - |
Homo sapiens | |
| 0.3535 | - |
Z-Lys-Leu-B(OH)2 | - |
Homo sapiens | |
| 0.4141 | - |
Z-Lys-Leu-Nle-H | - |
Homo sapiens | |
| 0.5 | - |
Z-SSKF(4-Br)L-H | - |
Homo sapiens | |
| 0.5 | - |
Z-YL-H | - |
Homo sapiens | |
| 1 | - |
Z-SSKLD-H | - |
Homo sapiens | |
| 1 | - |
Z-SSKL-H | - |
Homo sapiens | |
| 1 | - |
Z-KL-H | - |
Homo sapiens | |
| 1 | - |
Z-QL-H | - |
Homo sapiens | |
| 1 | - |
Z-Ser-Ser-Lys-Leu-D-Leu-H | - |
Homo sapiens | |
| 1 | - |
Z-Lys-Nle-H | - |
Homo sapiens | |
| 1 | - |
Z-Gln-Nle-H | - |
Homo sapiens | |
| 1 | - |
Z-Ser-Ser-Lys-Nle-H | - |
Homo sapiens | |
| 1 | - |
Z-Ser-Ser-Lys-Leu-D-Nle-H | - |
Homo sapiens | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | PSA-specific monoclonal antibodies block proteolysis of extracellular matrix components and decrease invasion of PSA-producing LNCaP cells in Matrigel invasion assays | down |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | PSA inhibits fibroblast growth factor mediated angiogenesis in a Matrigel plug assay. It can inactivate PTHrP-stimulated cAMP accumulation in mouse osteoblasts | Mus musculus |
| physiological function | role of PSA as a biomarker for prostate cancer, plays an important role in the pathobiology of prostate cancer. In primary cultures of prostatic epithelial cells, PSA activates specifically the small latent form of TGFbeta2. Active PSA can release cytokines involved in bone turnover such as insulin-like growth factor-1 and TGFbeta2. PSA can alter the bone metastatic phenotype from osteoclastic to osteoblastic through PTHrP degradation. Role for active PSA in preferential adhesion of prostate cancer cells to bone. PSA-expressing SaOS-2 cells markedly upregulate expression of genes associated with osteoblast differentiation including runx-2 and osteocalcin. PSA inhibits angiogenesis both in vitro and in vivo. Purified PSA inhibits human umbilical vein endothelial cell proliferation, migration, and invasion. PSA inhibits endothelial cell response to the angiogenic stimulators fibroblast growth factor 2 and vascular endothelial growth factor | Homo sapiens |
kcat/KM [mM/s]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 3900 | - |
Mca-QFYSSNK(epsilon-dinitrophenyl) | - |
Homo sapiens | |
| 23000 | - |
HSSKLQ-7-amido-4-methylcoumarin | - |
Homo sapiens | |
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