Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
enzyme PepP belongs to the family of proline-specific aminopeptidases
evolution
-
enzyme TgAPP is a member of the M24 prolyl aminopeptidase family
evolution
pepP encodes an enzyme belonging to the aminopeptidases P (APPro) family, a type of metalloprotease that catalyzes the removal of the N-terminal residue from a polypeptide that has proline as the second residue. Enzyme PepP is highly conserved in all Pseudomonas aeruginosa genomes sequenced to date and has high genetic similarity with enzymes from other Pseudomonas species (82.4%-100% identity)
evolution
the enzyme belongs to the M24B subfamily of aminoproteases
evolution
the enzyme belongs to the M24B subfamily of aminoproteases
evolution
the enzyme TvMP50 belong to the aminopeptidase P-like metalloproteinase subfamily A/B, family M24 of clan MG, Parabasalia group. The Parabasalia group contains two protein lineages with a pita bread fold; the ancestral monomeric group 1 is probably derived from an ancestral dimeric aminopeptidase P-type enzyme, and group 2 has a probable dimeric kind of ancestral eukaryotic prolidase lineage. Phylogenetic analysis, overview
evolution
-
enzyme TgAPP is a member of the M24 prolyl aminopeptidase family
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
evolution
-
the enzyme belongs to the M24B subfamily of aminoproteases
-
malfunction
in 2 families with an nephronophthisis-like phenotype, homozygous frameshift and splice-site mutations, respectively, are detected in the X-prolyl aminopeptidase 3 gene
malfunction
-
suppression of zebrafish xpnpep3 phenocopied the developmental phenotypes of ciliopathy morphants, and this effect is rescued by human XPNPEP3 that is devoid of a mitochondrial localization signal, suggesting that the protein might also have mitochondrial-independent activity
malfunction
-
Xpnpep1 knockout mice display severe growth retardation, microcephaly, and modest lethality. Imino-oligopeptide excretion is observed in urine samples from APP1-deficient mice
malfunction
-
deletion of TgAPP gene in the parasite through a CRISPR/Cas9 system results in inhibition of growth indicating the importance of TgAPP
malfunction
-
deletion of TgAPP gene in the parasite through a CRISPR/Cas9 system results in inhibition of growth indicating the importance of TgAPP
-
metabolism
-
four metalloaminopeptidases (MAPs) play a role in peptide turnover in Pf parasites: leucyl aminopeptidase (PfA-M17), alanyl aminopeptidase (PfA-M1), aspartyl aminopeptidase (PfM18AAP), and aminopeptidase P (PfAPP). The substrate profile shows that PfAPP has the capacity to catalyze the removal of any N-terminal amino acid residue from peptides with a P1' proline, and that the other MAPs in Plasmodium falciparum are unable to perform this function
metabolism
the genome of the unicellular cyanobacterium Synechocystis sp. PCC6803 contains 25 genes of aminopeptidases, among which only the sll0136 gene encodes a aminopeptidase P (PepP)
physiological function
eukaryotic aminopeptidase P1 (APP1) is a cytosolic exopeptidase that preferentially removes amino acids from the N-terminus of peptides possessing a penultimate N-terminal proline residue. The enzyme has an important role in the catabolism of proline containing peptides since peptide bonds adjacent to the imino acid proline are resistant to cleavage by most peptidases, role for APP-1 is in the breakdown of imino-peptides generated during protein catabolism
physiological function
-
peptide recycling, the process by which cellular proteins are broken down to single amino acid residues, is critical to parasite survival. In blood-stage malaria parasites, two major processes are responsible for peptide turnover: proteasomal (within the cytosol) and vacuolar (in the specialized digestive food vacuole). The vacuolar pathway is responsible for the digestion of 60-80% of host cell hemoglobin, which is imported into the digestive vacuole and degraded into free amino acids. This process is absolutely necessary for parasite growth and development. The final step of peptide turnover, the removal of N-terminal amino acids from short polypeptide chains, is catalyzed by a panel of aminopeptidases, which work in concert according to different substrate specificities, to complete protein digestion. During the blood stage, the parasites utilise a proteolytic cascade to digest host hemoglobin, which produces free amino acids absolutely necessary for parasite growth and reproduction. The enzymes required for hemoglobin digestion are therefore attractive therapeutic targets. The final step of the cascade is catalyzed by several metalloaminopeptidases, including aminopeptidase P (APP)
physiological function
Xaa-Pro aminopeptidase-1 is an anti-proliferative and anti-migratory exoprotease. Differential expression of Xaa-Pro aminopeptidases 1 and 2 in renal cancer, overview
additional information
analysis of structure-function relationship of aminopeptidase P, structure modelling, overview. A loop extending from the active site is important for specific large-substrate binding, and this non-conserved surface loop is also critical for Pseudomonas aeruginosa virulence. The extended substrate binding site is identified to be responsible for virulence-related protein recognition.
additional information
Caenorhabditis elegans APP-1 shares similar mode of substrate binding and a common catalytic mechanism with other known X-prolyl aminopeptidases
additional information
-
Caenorhabditis elegans APP-1 shares similar mode of substrate binding and a common catalytic mechanism with other known X-prolyl aminopeptidases
additional information
isozymes XPNPEP1 and -2 have comparable structural properties and similar substrate specificities
additional information
isozymes XPNPEP1 and -2 have comparable structural properties and similar substrate specificities
additional information
-
isozymes XPNPEP1 and -2 have comparable structural properties and similar substrate specificities
additional information
the active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
additional information
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
additional information
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-123) and a C-terminal domain (residues 124-360). The C-terminal domain, adopting a typical pita-bread-fold, houses the metal binding active site. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
additional information
three-dimensional modeling of the Synechocystis sp. PCC6803 PepP protein, overview. The PepP amino acid residues Asp260, Asp271, His354, Glu385, and Glu415 are involved in the formation of the enzym's catalytic site
additional information
-
three-dimensional structure analysis and structure-function analysis, structure comparisons, overview
additional information
Trichomonas vaginalis metalloproteinase TvMP50 is a monomeric aminopeptidase P-like enzyme
additional information
-
Trichomonas vaginalis metalloproteinase TvMP50 is a monomeric aminopeptidase P-like enzyme
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-
additional information
-
the protein adopts a two-domain structure typical of the M24B subfamily with an N-terminal domain (residues 1-121) and a C-terminal domain (residues 122-349). The C-terminal domain, adopting a typical pitabread-fold, houses the metal binding active site. Residues Asp53, Arg55, and Tyr56 are part of the conserved DXRY motif, which is important for enzymatic activity, His193 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substrates. Residue His93 is expected to interact with the DXRY motif in the closed conformation and may also be involved in substrate binding, His281 is expected to be part of the proline binding pocket, and Arg298 is expected to interact with tripeptide and longer peptide substratesBoth His281 and Arg298 residues are found to be disordered in the Dr-smAPP structure. The active site includes the DXRY motif. Structure comparisons of small aminopeptidases-P
-