Any feedback?
Literature summary extracted from
- Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations (2008), Amino Acids, 35, 739-752.
Activating Compound
| EC Number | Activating Compound | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.13.9 | additional information | phosphorylation at four S109, S134, S198, S236, one T86, and two Y117, Y124 putative sites for phosphorylation, mediated respectively by Mapk pathway and NO/cGMP signaling, upregulate prolidase activity | Homo sapiens | |
| 3.4.13.9 | NO | NO stimulate both prolidase activity and collagen biosynthesis in fibroblasts, increase in the enzyme activity is due to increase in the enzyme phosphorylation on serine/threonine residue | Homo sapiens |  |
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 3.4.13.9 | drug development | the enzyme is used as target enzyme for specific melanoma prodrug activation | Homo sapiens |
| 3.4.13.9 | food industry | prolidase can be used in dietary industry as bitterness reducing agent | Homo sapiens |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 3.4.13.9 | DNA and amino acid sequence determination and anaylsis | Pyrococcus furiosus |
| 3.4.13.9 | expression of wild-type and mutant enzymes in Escherichia coli, CHO cells, Pichia pastoris, or Saccharomyces cerevisiae, DNA and amino acid sequence determination and anaylsis, recombinant human prolidase expressed in Pichia pastoris catalyzes the hydrolysis of organophosphorus compounds as well as the digestion of Gly-Pro dipeptides | Homo sapiens |
| 3.4.13.9 | gene PEPD, localized on chromosome 19, genetic structure and organization, expression in CHO cells and in colorectal cancer cells | Homo sapiens |
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 3.4.13.9 | enzyme with bound Zn2+ substituting Co2+ | Pyrococcus furiosus |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.4.13.9 | G278D | naturally occuring point mutation causing prolidase deficiency | Homo sapiens |
| 3.4.13.9 | G448R | naturally occuring point mutation causing prolidase deficiency | Homo sapiens |
| 3.4.13.9 | additional information | complete map of the known PEPD mutant alleles causing prolidase deficiency, which is a rare recessive disorder characterized by severe skin lesions, single amino acid substitutions, exon splicing, deletions and a duplication are described as causative for the disease and are mainly located at highly conserved amino acids in the sequence of prolidase, genotype-phenotype correlation, clinical phenotype, overview | Homo sapiens |
| 3.4.13.9 | R184Q | naturally occuring point mutation causing prolidase deficiency | Homo sapiens |
| 3.4.13.9 | R265X | naturally occuring point mutation causing prolidase deficiency | Homo sapiens |
| 3.4.13.9 | R276N | naturally occuring point mutation causing prolidase deficiency | Homo sapiens |
| 3.4.13.9 | S202F | naturally occuring point mutation causing prolidase deficiency | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.13.9 | NiCl2 | - |
Homo sapiens | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 3.4.13.9 | cytosol | - |
Homo sapiens | 5829 | - |
| 3.4.13.9 | intracellular | dipeptidase function | Homo sapiens | 5622 | - |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.13.9 | Co2+ | metalloenzyme, required for activity, a homodimer having one Co-bound dinuclear metal cluster per monomer with one tightly bound Co1 and one loosely bound Co2 cobalt site, 5 amino acids that function as metal-binding residues: His284 and Glu313 solely bind to the first cobalt centre, Co1, Asp209 to the second cobalt centre, Co2, and Asp220 and Glu327 to both Co2+ ions | Pyrococcus furiosus | |
| 3.4.13.9 | Mn2+ | metalloenzyme, required for activity, each subunit contains two ions Mn2+, binding structure, overview | Homo sapiens | |
| 3.4.13.9 | Mn2+ | metalloenzyme, required for activity, the active site Mn2+ cation is simultaneously ligated to the prolyl carboxyl group and the amido oxygen of the preceding residue of the trans X-Pro dipeptides | Homo sapiens | |
| 3.4.13.9 | Na+ | the enzyme contains five Na+ ions, four organized in two dinuclear centres and one located in an external position of the homodimer, each subunit contains two ions Na+, binding structure, overview | Homo sapiens | |
Molecular Weight [Da]
| EC Number | Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|---|
| 3.4.13.9 | 54305 | - |
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli | Homo sapiens |
| 3.4.13.9 | 56000 | - |
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli | Homo sapiens |
| 3.4.13.9 | 57000 | - |
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli | Homo sapiens |
| 3.4.13.9 | 58000 | - |
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli | Homo sapiens |
| 3.4.13.9 | 73000 | - |
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli | Homo sapiens |
| 3.4.13.9 | 123000 | - |
recombinant enzyme from Escherichia coli | Homo sapiens |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.4.13.9 | additional information | Homo sapiens | the enzyme is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling, overview, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and is used as target enzyme for specific melanoma prodrug activation, prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions, overview | ? | - |
? | |
| 3.4.13.9 | additional information | Homo sapiens | the enzyme plays an important role in the recycling of proline from imidodipeptides, mostly derived from degradation products of collagen, for resynthesis of collagen and other proline-containing proteins, prolidase-dependent regulation of collagen biosynthesis, pathogenic mechanisms in enzyme deficiency, overview | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.4.13.9 | Homo sapiens | - |
- |
- |
| 3.4.13.9 | Homo sapiens | - |
gene PEPD | - |
| 3.4.13.9 | Pyrococcus furiosus | - |
- |
- |
Posttranslational Modification
| EC Number | Posttranslational Modification | Comment | Organism |
|---|---|---|---|
| 3.4.13.9 | glycoprotein | prolidase contains two putative site for N-glycosylation at N13 and N172, and one putative site for O-glycosylation at T458, about 0.5% of carbohydrate content | Homo sapiens |
| 3.4.13.9 | phosphoprotein | enzyme phosphorylation on serine/threonine residue activating the enzyme | Homo sapiens |
| 3.4.13.9 | phosphoprotein | four S109, S134, S198, S236, one T86, and two Y117, Y124 putative sites for phosphorylation, prolidase is both a phosphotyrosine and a phosphothreonine/serine enzyme, both phosphorylations, mediated respectively by Mapk pathway and NO/cGMP signaling, upregulate prolidase activity | Homo sapiens |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 3.4.13.9 | recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography, removal of His-tag by factor Xa | Homo sapiens |
Reaction
| EC Number | Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|---|
| 3.4.13.9 | hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro | catalytic mechanism and active site structure | Homo sapiens | |
| 3.4.13.9 | hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro | catalytic mechanism and active site structure | Pyrococcus furiosus |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 3.4.13.9 | erythrocyte | - |
Homo sapiens | - |
| 3.4.13.9 | fibroblast | - |
Homo sapiens | - |
| 3.4.13.9 | kidney | - |
Homo sapiens | - |
| 3.4.13.9 | leukocyte | - |
Homo sapiens | - |
| 3.4.13.9 | liver | - |
Homo sapiens | - |
| 3.4.13.9 | melanoma cell | higher expression of prolidase in tumor cells and particularly in melanoma cells | Homo sapiens | - |
| 3.4.13.9 | placenta | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.4.13.9 | Ala-Pro + H2O | - |
Homo sapiens | Ala + Pro | - |
? | |
| 3.4.13.9 | Ala-Pro + H2O | enzyme-substrate interaction model | Homo sapiens | Ala + Pro | - |
? | |
| 3.4.13.9 | Gly-Pro + H2O | - |
Pyrococcus furiosus | Gly + Pro | - |
? | |
| 3.4.13.9 | Gly-Pro + H2O | preferred substrate | Homo sapiens | Gly + Pro | - |
? | |
| 3.4.13.9 | Leu-Pro + H2O | - |
Homo sapiens | Leu + Pro | - |
? | |
| 3.4.13.9 | Met-Pro + H2O | - |
Homo sapiens | Met + Pro | - |
? | |
| 3.4.13.9 | additional information | the enzyme is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling, overview, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and is used as target enzyme for specific melanoma prodrug activation, prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions, overview | Homo sapiens | ? | - |
? | |
| 3.4.13.9 | additional information | the enzyme plays an important role in the recycling of proline from imidodipeptides, mostly derived from degradation products of collagen, for resynthesis of collagen and other proline-containing proteins, prolidase-dependent regulation of collagen biosynthesis, pathogenic mechanisms in enzyme deficiency, overview | Homo sapiens | ? | - |
? | |
| 3.4.13.9 | additional information | prolidase is an unusual metalloenzyme that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end, it is a dipeptidase able to hydrolyse the peptide bond in dipeptides containing respectively a N- or C-terminal proline or hydroxyproline residue, overview, recombinant human prolidase expressed in Pichia pastoris catalyzes the hydrolysis of organophosphorus compounds as well as the digestion of Gly-Pro dipeptides | Homo sapiens | ? | - |
? | |
| 3.4.13.9 | additional information | substrate specificity, prolidase is a cytosolic imidodipeptidase, which specifically splits imidodipeptides with C-terminal proline or hydroxyproline, overview | Homo sapiens | ? | - |
? | |
| 3.4.13.9 | Phe-Pro + H2O | - |
Homo sapiens | Phe + Pro | - |
? | |
| 3.4.13.9 | Val-Pro + H2O | - |
Homo sapiens | Val + Pro | - |
? | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 3.4.13.9 | dimer | 2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli | Homo sapiens |
| 3.4.13.9 | dimer | crystal structure analysis, active site analysis, overview | Pyrococcus furiosus |
| 3.4.13.9 | More | crystal structure and active site organization, overview | Homo sapiens |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.4.13.9 | PepD | - |
Homo sapiens |
| 3.4.13.9 | peptidase D | - |
Homo sapiens |
| 3.4.13.9 | prolidase | - |
Homo sapiens |
| 3.4.13.9 | prolidase | - |
Pyrococcus furiosus |
Temperature Optimum [°C]
| EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|---|
| 3.4.13.9 | 37 | 50 | native enzyme | Homo sapiens |
| 3.4.13.9 | 50 | - |
recombinant enzyme | Homo sapiens |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 3.4.13.9 | 7.8 | - |
- |
Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
