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Information on EC 3.4.24.64 - mitochondrial processing peptidase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P10507
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3.4.24.64 mitochondrial processing peptidaseSpecify your search results
Word Map
- 3.4.24.64
- presequence
-
nuclear-encoded
- preproteins
-
intermembrane
- frataxin
- metalloendopeptidase
-
friedreich
-
matrix-targeting
-
hxxeh
- mas1
- plumbaginifolia
-
nuclearly
-
matrix-localized
-
intermediate-sized
- agriculture
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
mitochondrial processing peptidase, beta-mpp, alpha-mpp, processing peptidase, matrix processing peptidase, atp23, mitochondrial processing protease, processing enhancing protein, general mitochondrial processing peptidase, pmpca, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Alpha-MPP
-
-
-
-
Beta-MPP
-
-
-
-
General mitochondrial processing peptidase
-
-
-
-
HA1523
-
-
-
-
Matrix peptidase
-
-
-
-
Matrix processing peptidase
-
-
-
-
Matrix processing proteinase
-
-
-
-
Mitochondrial chelator-sensitive protease
-
-
-
-
Mitochondrial protein precursor-processing proteinase
-
-
-
-
MPP
P-52
-
-
-
-
P-55
-
-
-
-
Processing enhancing peptidase
-
-
-
-
Proteinase, mitochondrial protein precursor-processing
-
-
-
-
MPP
-
-
-
-
MPP
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Release of N-terminal targetting peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2
Release of N-terminal targetting peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2
mechanism
-
Release of N-terminal targetting peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2
limited proteolysis: cleaves precursors of mitochondrial proteins to their mature form, not further
-
Release of N-terminal targetting peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2
cleaves amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins
-
Release of N-terminal targetting peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2
the amino acid residues on the C-terminal side of the cleavage site in the preprotein are orientated tail out from the large cavity of MPP and interact with the glycine-rich loop of the alpha-MPP subunit. Thus, MPP orientates preproteins at the specific cleft between the catalytic domain and the flexible glycine-rich loop, which seems to pinch the extended polypeptide, catalytic mechanism, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
86280-61-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
composite precursor protein Atp25 + H2O
?
-
homologue protein of the bacterial ribosome-silencing factor (Rsf) is generated from the composite precursor protein Atp25 upon internal cleavage by the matrix processing peptidase MPP. In vitro incubation of Atp25 with purified MPP results in three fragments resembling the MTS, the Rsf, and the M domain
-
-
?
Cytochrome c oxidase subunit IV precursor + H2O
Cytochrome c oxidase subunit IV
-
-
-
?
epidermal growth factor receptor preprotein + H2O
mature epidermal growth factor receptor + prepeptide of epidermal growth factor receptor
F1-ATPase beta-subunit precursor + H2O
F1-ATPase beta-subunit
-
-
-
-
?
MAS1 precursor + H2O
MAS1
-
MAS1 takes part in its own precursor activation
-
?
Mitochondrial alcohol dehydrogenase precursor + H2O
Mitochondrial alcohol dehydrogenase
-
-
-
?
mitochondrial malate dehydrogenase precursor + H2O
mitochondrial malate dehydrogenase + mitochondrial malate dehydrogenase transit peptide
-
the extreme C-terminus of the alpha-subunit of mitochondrial processing peptidase provides mechanical support to the C-terminal domain of the protein during its extensive conformational change accompanying the substrate recognition site
-
-
?
Mitochondrial proteins with artificial precursors + H2O
?
-
containing presequence of ATPase subunit 9 fused to dehydrofolate reductase, i.e. pre-Su9-DHFR
-
-
?
P-25 peptide + H2O
?
-
matrix-targeting peptide containing cleavage site of authentic precursor protein
-
-
?
plant mitochondrial carrier proteins + H2O
?
-
yeast mitochondria process the plant mitochondrial carrier protein to the same intermediate size as purified plant MPP. This intermediary processing does not occur in a temperature sensitive yeast mutant for MPP at the restrictive temperature
-
-
?
Precytochrome b2-mouse dehydrofolate reductase fusion protein + H2O
31-aminoacid presequence + cytochrome b2-mouse dehydrofolate reductase protein
-
-
-
-
?
preprotein Din7 + H2O
presequence + protein Din7
-
-
-
?
preprotein Mrx8 + H2O
presequence + protein Mrx8
-
-
-
?
preprotein Yhb1 + H2O
presequence + protein Yhb1
-
-
-
?
presequence-containing protein + H2O
presequence + protein
-
-
-
-
?
Cytochrome b2 precursor + H2O
Cytochrome b2 intermediate form
-
-
-
?
Cytochrome b2 precursor + H2O
Cytochrome b2 intermediate form
-
-
-
?
Cytochrome b2 precursor + H2O
Cytochrome b2 intermediate form
-
-
-
?
Cytochrome c oxidase subunit V precursor + H2O
Cytochrome c oxidase subunit V
-
-
-
?
Cytochrome c oxidase subunit V precursor + H2O
Cytochrome c oxidase subunit V
-
-
-
?
Cytochrome c1 precursor + H2O
Cytochrome c1 intermediate form
-
membrane-bound enzyme
-
-
?
Cytochrome c1 precursor + H2O
Cytochrome c1 intermediate form
-
membrane-bound enzyme
-
?
Cytochrome c1 precursor + H2O
Cytochrome c1 intermediate form
-
membrane-bound enzyme
-
?
epidermal growth factor receptor preprotein + H2O
mature epidermal growth factor receptor + prepeptide of epidermal growth factor receptor
-
-
-
-
?
epidermal growth factor receptor preprotein + H2O
mature epidermal growth factor receptor + prepeptide of epidermal growth factor receptor
-
analysis of the fluorescence resonance energy transfer between EGFP fused to a yeast aconitase presequence and regiospecific 7-dietylamino-3-(4'-maleimidyl phenyl)-4-methyl coumarin-labelled yeast MPPs, overview
-
-
?
F1-ATPase alpha-subunit precursor + H2O
F1-ATPase alpha-subunit
-
-
-
?
F1-ATPase alpha-subunit precursor + H2O
F1-ATPase alpha-subunit
-
-
-
?
Nfs1 + H2O
processed Nfs1
-
MPP cleaves the precursor between Phe33 and Tyr34, Nfs1 processing, overview
-
-
?
Nfs1 + H2O
processed Nfs1
-
recombinant His-tagged substrate. Nfs1 is a highly conserved mitochondrial cysteine desulfurase with dual localization in mitochondria and nuclei, mechanism of Nfs1 distribution, overview
-
-
?
nuclear-encoded polyprotein precursor + H2O
?
-
the nuclear-encoded protein RPS14 (ribosomal protein S14) of rice mitochondria is synthesized in the cytosol as a polyprotein consisting of a large N-terminal domain comprising preSDHB (succinate dehydrogenase B precursor) and the C-terminal RPS14. After the preSDHBRPS14 polyprotein is transported into the mitochondrial matrix, the protein is processed into three peptides: the N-terminal prepeptide, the SDHB domain and the C-terminal mature RPS14. MPP (mitochondrial processing peptidase) plays an essential role in processing of the polyprotein. Purified yeast MPP cleaves both the N-terminal presequence and the connector region between SDHB and RPS14. The connector region is processed more rapidly than the presequence. The cleavage site between SDHB and RPS14 is located in an MPPprocessing motif. MPP interacts with multiple sites in the region, possibly in a similar manner to the interaction with the N-terminal presequence. In addition, MPP preferentially recognizes the unfolded structure of preSDHBRPS14. In mitochondria, MPP may recognize the stretched poly-protein during passage of the precursor through the translocational apparatus in the inner membrane, and cleaves the connecting region between the SDHB and RPS14 domains even before processing of the presequence
-
-
?
nuclear-encoded polyprotein precursor + H2O
?
-
the nuclear-encoded protein RPS14 (ribosomal protein S14) of rice mitochondria is synthesized in the cytosol as a polyprotein consisting of a large N-terminal domain comprising preSDHB (succinate dehydrogenase B precursor) and the C-terminal RPS14. After the preSDHBRPS14 polyprotein is transported into the mitochondrial matrix, the protein is processed into three peptides: the N-terminal prepeptide, the SDHB domain and the C-terminal mature RPS14. MPP (mitochondrial processing peptidase) plays an essential role in processing of the polyprotein. Purified yeast MPP cleaves both the N-terminal presequence and the connector region between SDHB and RPS14. The connector region is processed more rapidly than the presequence. The cleavage site between SDHB and RPS14 is located in an MPP processing motif. MPP interacts with multiple sites in the region, possibly in a similar manner to the interaction with the N-terminal presequence. In addition, MPP preferentially recognizes the unfolded structure of preSDHBRPS14. In mitochondria, MPP may recognize the stretched poly-protein during passage of the precursor through the translocational apparatus in the inner membrane, and cleaves the connecting region between the SDHB and RPS14 domains even before processing of the presequence
-
-
?
pre-F1FO-ATP synthase + H2O
mature F1FO-ATP synthase + prepeptide
-
on one hand, Atp23 serves as a processing peptidase and mediates the maturation of the mitochondrially-encoded FO-subunit Atp6 after its insertion into the inner membrane, on the other hand, independent of its proteolytic activity, Atp23 promotes the association of mature Atp6 with Atp9 oligomers with chaperone activity, overview, the assembly step is thus under the control of two substrate-specific chaperones, Atp10 and Atp23, which act on opposite sides of the inner membrane, modelling of assembly, overview
-
-
?
pre-F1FO-ATP synthase + H2O
mature F1FO-ATP synthase + prepeptide
-
putative catalytically active Glu168
-
-
?
additional information
?
-
-
the large subunit alone has no cleavage activity
-
-
?
additional information
?
-
-
alpha-MPP (formerly MAS2) alone has no catalytic activity
-
-
?
additional information
?
-
-
No substrates are several non-mitochondrial proteins
-
-
?
additional information
?
-
-
No substrates are several non-mitochondrial proteins
-
-
?
additional information
?
-
-
e.g. bovine serum albumin, mouse immunoglobulin G, yeast hexokinase or yeast tryptophan synthase, neither in native nor in heat or pH-denatured form
-
-
?
additional information
?
-
-
No substrates are mature mitochondrial proteins
-
-
?
additional information
?
-
-
precursor substrates must be synthesized by translation in a mRNA-dependent in vitro translation system, e.g. nuclease-treated rabbit reticulocyte lysate
-
-
?
additional information
?
-
-
No substrates are denatured enzyme precursors
-
-
?
additional information
?
-
-
MAS2 activity alone is very low, MAS1 restores activity
-
-
?
additional information
?
-
-
substrate binds to MAS2, not MAS1 enzyme component (photocrosslinking experiment)
-
-
?
additional information
?
-
-
substrate binding changes conformation of the alpha-subunit
-
?
additional information
?
-
-
removes amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins during or after translocation across mitochondrial membranes
-
-
?
additional information
?
-
-
removes amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins during or after translocation across mitochondrial membranes
-
-
?
additional information
?
-
-
removes amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins during or after translocation across mitochondrial membranes
-
-
?
additional information
?
-
-
plays an essential role in mitochondrial protein import
-
?
additional information
?
-
-
the enzyme genetically interacts with prohibitins in the inner mitochondrial membrane and links the function of prohibitins to the F1FO-ATP synthase complex
-
-
?
additional information
?
-
-
the enzyme specifically recognizes mitochondrial preproteins and removes their basic N-terminal signal prepeptides
-
-
?
additional information
?
-
-
the mitochondrial processing peptidase removes leader peptides of preproteins after import into the mitochondrial matrix space to increase protein stability, enzyme inhibition leads to degradation of the unprocessed preproteins in the mitochondrial matrix space, overview
-
-
?
additional information
?
-
-
the enzyme specifically recognizes mitochondrial preproteins and removes their basic N-terminal signal prepeptides, overview
-
-
?
additional information
?
-
-
cleavage site specificity of the major mitochondrial processing peptidase for removal of N-terminal presequences from mitochondrial proteins during maturation, global analysis of the N-proteome of yeast mitochondria, method, overview. For a number of proteins such as Gif1 and Pdb1, more than one N-terminus exist, therefore two truncated versions of the proteins are synthesized and compared to the in organello processing product, product identification by LC-MS/MS analysis
-
-
?
additional information
?
-
-
construction of a mutant MPP recognition sequence in substrate Nfs1 by replacing the two arginine codons at positions -2 and -3 prevents cleavage by MPP
-
-
?
additional information
?
-
quantitative ChaFRADIC (charge-based fractional diagonal chromatography) analysis identifies 66 novel substrate proteins, which allow refinement of the MPP cleavage site establishing R2 as a major determinant of mitochondrial processing protease recognition and processing. Proteins that do not posses a presequence are not substrates
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
epidermal growth factor receptor preprotein + H2O
mature epidermal growth factor receptor + prepeptide of epidermal growth factor receptor
-
-
-
-
?
Nfs1 + H2O
processed Nfs1
-
MPP cleaves the precursor between Phe33 and Tyr34, Nfs1 processing, overview
-
-
?
nuclear-encoded polyprotein precursor + H2O
?
-
the nuclear-encoded protein RPS14 (ribosomal protein S14) of rice mitochondria is synthesized in the cytosol as a polyprotein consisting of a large N-terminal domain comprising preSDHB (succinate dehydrogenase B precursor) and the C-terminal RPS14. After the preSDHBRPS14 polyprotein is transported into the mitochondrial matrix, the protein is processed into three peptides: the N-terminal prepeptide, the SDHB domain and the C-terminal mature RPS14. MPP (mitochondrial processing peptidase) plays an essential role in processing of the polyprotein. Purified yeast MPP cleaves both the N-terminal presequence and the connector region between SDHB and RPS14. The connector region is processed more rapidly than the presequence. The cleavage site between SDHB and RPS14 is located in an MPPprocessing motif. MPP interacts with multiple sites in the region, possibly in a similar manner to the interaction with the N-terminal presequence. In addition, MPP preferentially recognizes the unfolded structure of preSDHBRPS14. In mitochondria, MPP may recognize the stretched poly-protein during passage of the precursor through the translocational apparatus in the inner membrane, and cleaves the connecting region between the SDHB and RPS14 domains even before processing of the presequence
-
-
?
pre-F1FO-ATP synthase + H2O
mature F1FO-ATP synthase + prepeptide
-
on one hand, Atp23 serves as a processing peptidase and mediates the maturation of the mitochondrially-encoded FO-subunit Atp6 after its insertion into the inner membrane, on the other hand, independent of its proteolytic activity, Atp23 promotes the association of mature Atp6 with Atp9 oligomers with chaperone activity, overview, the assembly step is thus under the control of two substrate-specific chaperones, Atp10 and Atp23, which act on opposite sides of the inner membrane, modelling of assembly, overview
-
-
?
presequence-containing protein + H2O
presequence + protein
-
-
-
-
?
additional information
?
-
-
removes amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins during or after translocation across mitochondrial membranes
-
-
?
additional information
?
-
-
removes amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins during or after translocation across mitochondrial membranes
-
-
?
additional information
?
-
-
removes amino-terminal matrix-targeting sequences from imported mitochondrial precursor proteins during or after translocation across mitochondrial membranes
-
-
?
additional information
?
-
-
plays an essential role in mitochondrial protein import
-
?
additional information
?
-
-
the enzyme genetically interacts with prohibitins in the inner mitochondrial membrane and links the function of prohibitins to the F1FO-ATP synthase complex
-
-
?
additional information
?
-
-
the enzyme specifically recognizes mitochondrial preproteins and removes their basic N-terminal signal prepeptides
-
-
?
additional information
?
-
-
the mitochondrial processing peptidase removes leader peptides of preproteins after import into the mitochondrial matrix space to increase protein stability, enzyme inhibition leads to degradation of the unprocessed preproteins in the mitochondrial matrix space, overview
-
-
?
additional information
?
-
-
cleavage site specificity of the major mitochondrial processing peptidase for removal of N-terminal presequences from mitochondrial proteins during maturation, global analysis of the N-proteome of yeast mitochondria, method, overview. For a number of proteins such as Gif1 and Pdb1, more than one N-terminus exist, therefore two truncated versions of the proteins are synthesized and compared to the in organello processing product, product identification by LC-MS/MS analysis
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Mn2+
Zn2+
additional information
additional information
-
metalloendopeptidase that does not contain His-Glu-X-X-His zinc-binding motif, cf. human insulinase or E. coli protease III
additional information
-
atomic absorption spectroscopy: purified MAS1/MAS2-holoenzyme lacks significant amounts of zinc, manganese or cobalt, probably lost during purification
additional information
-
consensus metal-binding motif HEliH, formed by amino acid residues 167-171 of Atp23
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
o-phenanthroline
-
enzyme inhibition leads to degradation of the unprocessed preproteins in the mitochondrial matrix space
Prepeptide p25
-
derived from amino terminal of cytochrome oxidase subunit IV precursor, kinetics
Prepeptide p34
-
derived from amino terminal of cytochrome oxidase subunit IV precursor, kinetics
1,10-phenanthroline
-
excess Zn2+ or Co2+ partially restores; soluble matrix enzyme
1,10-phenanthroline
-
excess Zn2+ or Co2+ partially restores; in vitro and in vivo
EDTA
-
excess Co2+ restores; excess Mn2+ restores; excess Zn2+, Co2+ partially restores
GTP
-
soluble matrix enzyme; Zn2+ or Co2+ in excess partially restores
additional information
-
isolated from dog; no inhibition by chymotryptic inhibitors; no inhibition by leupeptin or pepstatin; no inhibition by serine protease inhibitors, e.g. antipain, chymostatin; no inhibition by tryptic inhibitors; pancreas, chicken egg white or soybean
-
additional information
-
4-aminobenzamidine; tosyl-Lys chloromethyl ketone, tosyl-Phe chloromethyl ketone
-
additional information
-
4-aminobenzamidine; diisopropyl fluoride; isolated from bovine; no inhibition by leupeptin or pepstatin; no inhibition by serine protease inhibitors, e.g. antipain, chymostatin; no inhibition by tryptic inhibitors; pancreas, chicken egg white or soybean; PMSF
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
half-maximal processing of in vitro synthesized precursors to their respective mature forms: F1-ATPase beta-subunit at 1.5 min, cytochrome b2 at 22 min and cytochrome c oxidase at 4 min
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23.44
-
strain JKR 102(YEp13-MAS1 plus pCF35-MAS2), overexpressing MAS1 and MAS2
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
P10507: mitochondrial-processing peptidase subunit beta (MAS1), P11914: mitochondrial-processing peptidase subunit alpha (MAS2)
SwissProt
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
Nfs1 needs to be processed by MPP to be functional in the mitochondrion and the nucleus, the latter case requires a mechanism that involves reverse translocation of processed Nfs1, i.e. the retrograde movement of Nfs1
-
-
-
-
matrix
-
MAS1 becomes insoluble in the absence of MAS2, presumably by aggregation
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
analysis of the mas1 mutant (temperature-sensitive mas1 mutant strain in which mitochondrial processing protease (MPP) is inactive when the cells are shifted to growth at nonpermissive temperature (37 °C)) reveales an increase in protein levels of nonprocessed mitochondrial proteins as well as an elevated membrane potential and increased oxygen consumption in mas1 mitochondria upon growth at nonpermissive temperature is observed. These findings might point toward a response in mas1 cells triggered to counterbalance the proteotoxic stress induced by MPP dysfunction
metabolism
-
yeast Nfs1 undergoes two steps of proteolytic processing: first it is cleaved by the mitochondrial processing peptidase, MPP, which removes its mitochondrial targeting sequence, and then it is cleaved by a peptidase, designated Icp55, which removes three amino acids from its N-terminus
physiological function
-
the mitochondrial processing protease is required in maturation of mitochondrial proproteins for removal of the N-terminal presequences
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
48000
48800
-
1 * 48800 (MAS1) + 1 * 51800 (MAS2), Saccharomyces cerevisiae, calculated from amino acid sequence
50000
51000
51800
-
1 * 48800 (MAS1) + 1 * 51800 (MAS2), Saccharomyces cerevisiae, calculated from amino acid sequence
52000
-
analytical sedimentation velocity ultracentrifugation at 20000 rpm, at lower speed aggregates of MW 90000 and MW 240000 occur
additional information
-
amino acid sequence comparison on the basis of statistical analysis, FASTP program
48000
-
1 * 48000 (MAS1) + 1 * 51000 (MAS2), Saccharomyces cerevisiae, SDS-PAGE
51000
-
isoform MAS2, SDS-PAGE, isoform MAS1, predicted from DNA sequence
51000
-
1 * 48000 (MAS1) + 1 * 51000 (MAS2), Saccharomyces cerevisiae, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
heterodimer
additional information
dimer
-
1 * 48000 (MAS1) + 1 * 51000 (MAS2), Saccharomyces cerevisiae, SDS-PAGE
dimer
-
1 * 48800 (MAS1) + 1 * 51800 (MAS2), Saccharomyces cerevisiae, calculated from amino acid sequence
dimer
-
MPP is a heterodimeric enzyme consisting of regulatory alpha-MPP and catalytic beta-MPP subunits, analysis of the fluorescence resonance energy transfer between EGFP fused to a yeast aconitase presequence and regiospecific 7-dietylamino-3-(4'-maleimidyl phenyl)-4-methyl coumarin-labelled yeast MPPs, plausible model of preEGFP associated with MPP constructed in silico, structure modeling, overview
heterodimer
-
consists of a alpha-mitochondrial processing peptidase and beta-MPP
additional information
-
alpha-MPP (formerly MAS2) alone has no catalytic activity
additional information
-
MAS2 activity alone is very low, MAS1 restores activity
additional information
-
Saccharomyces cerevisiae has two loosely associated non-identical subunits that dissociate upon gel filtration
additional information
-
homology between MAS1 and MAS2 amino acid sequences
additional information
-
the large subunit alone has no cleavage activity
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant MPP complexed with 2 different synthtic peptide substrates, crystallized by hanging-drop vapor diffusion method, unit cell constants a = 133 A, b = 178 A, c = 201 A, space group P2(1)2(1)2(1)
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
delW481-F482
-
mutation has no effect on protein solubility, slightly unstable during long-term storage
E168Q
-
site-directed mutation in the consensus metal-binding site, the active site residue mutant is proteolytically inactive, but shows processing of the Atp6 subunit of pre-F1FO-ATP synthase
E73Q
H167A
-
site-directed mutation in the consensus metal-binding site, the mutant does not show processing of the Atp6 subunit of pre-F1FO-ATP synthase
H171A
-
site-directed mutation in the consensus metal-binding site, the mutant does not show processing of the Atp6 subunit of pre-F1FO-ATP synthase
additional information
E73Q
-
site-directed mutagenesis, active site mutant, forms dimers like the wild-type enzyme
additional information
-
construction of a EGFP fused to a yeast aconitase presequence and 7-dietylamino-3-(4'-maleimidyl phenyl)-4-methyl coumarin-labelled yeast MPPs for fluorescence resonance energy transfer analysis
additional information
-
deletion of ATP23 completely inhibits the assembly of the mitochondrial-encoded FO-subunits into the F1FO-ATP synthase, which is observed in wild-type mitochondria
additional information
-
yeast aldehyde dehydrogenase and malate dehydrogenase are mutated so that they would not be processed by the enzyme after import into the mitochondrial matrix space, the mutant nonprocessed enzymes are functional but instable, the nonprocessed precursors are degraded in the matrix space, expression in HWTHL10 cells, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Separation of the loosely associated subunits of MW 48000 and 51000 causes complete loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
if MAS1 is overproduced in the absence of MAS2 it is insoluble and not suitable for purification, it is therefore purified from the purified holoenzyme
-
native enzyme partially by purification of mitochondria via sucrose gradient centrifugation
-
recombinant alpha- and beta-subunit separatly and as holoenzyme from Escherichia coli lysate
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
alpha-MPP expressed in soluble monomeric form combined with rat beta-MPP, each subunit gene cloned into an expression vector pTrc99A and transformed into Escherichia coli BL21(DE3)
-
cDNA of the precursor form of alpha and beta-MPP expressed in Escherichia coli BL21
-
coexpression of both subunits results in functionally active enzyme
-
expression of wild-type enzyme and enzyme mutants in DELTA atp23cells
-
wild-type and mutant enzyme overexpressed in Escherichia coli BL21(DE3)
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rawlings, N.D.; Barrett, A.J.
Homologues of insulinase, a new superfamily of metalloendopeptidases
Biochem. J.
275
389-391
1991
Neurospora crassa, Saccharomyces cerevisiae
Kalousek, F.; Neupert, W.; Omura, T.; Schatz, G.; Schmitz, U.K.
Uniform nomenclature for the mitochondrial peptidases cleaving precursors of mitochondrial proteins
Trends Biochem. Sci.
18
249
1993
Saccharomyces cerevisiae, Neurospora crassa, Rattus norvegicus, Solanum tuberosum
Bhni, P.C.; Daum, G.
Processing of mitochondrial polypeptide precursors in yeast
Methods Enzymol.
97
311-323
1983
Saccharomyces cerevisiae, Saccharomyces cerevisiae D-273-10B
McAda, P.C.; Douglas, M.G.
A yeast mitochondrial chelator-sensitive protease that processes cytoplasmically synthesized protein precursors: isolation from yeast and assay
Methods Enzymol.
97
337-344
1983
Saccharomyces cerevisiae
Bhni, P.C.; Daum, G.; Schatz, G.
Import of proteins into mitochondria. Partial purification of a matrix-located protease involved in cleavage of mitochondrial precursor polypeptides
J. Biol. Chem.
258
4937-4943
1983
Saccharomyces cerevisiae, Saccharomyces cerevisiae D-273-10B
Yang, M.; Jensen, R.E.; Yaffe, M.P.; Oppliger, W.; Schatz, G.
Import of proteins into yeast mitochondria: the purified matrix processing protease contains two subunits which are encoded by the nuclear MAS1 and MAS2 genes
EMBO J.
7
3857-3862
1988
Saccharomyces cerevisiae, Saccharomyces cerevisiae D-273-10B
Jensen, R.E.; Yaffe, M.P.
Import of proteins into yeast mitochondria: the nuclear MAS2 gene encodes a component of the processing protease that is homologous to the MAS1-encoded subunit
EMBO J.
7
3863-3871
1988
Saccharomyces cerevisiae
Witte, C.; Jensen, R.E.; Yaffe, M.P.; Schatz, G.
MAS1, a gene essential for yeast mitochondrial assembly, encodes a subunit of the mitochondrial processing protease
EMBO J.
7
1439-1447
1988
Saccharomyces cerevisiae, More
Geli, V.; Yang, M.; Suda, K.; Lustig, A.; Schatz, G.
The MAS-encoded processing protease of yeast mitochondria. Overproduction and characterization of its two nonidentical subunits
J. Biol. Chem.
265
19216-19222
1990
Saccharomyces cerevisiae
Yang, M.; Geli, V.; Oppliger, W.; Suda, K.; James, P.; Schatz, G.
The MAS-encoded processing protease of yeast mitochondria. Interaction of the purified enzyme with signal peptides and a purified precursor protein
J. Biol. Chem.
266
6416-6423
1991
Saccharomyces cerevisiae
Geli, V.
Functional reconstitution in Escherichia coli of the yeast mitochondrial matrix peptidase from its two inactive subunits
Proc. Natl. Acad. Sci. USA
90
6247-6251
1993
Saccharomyces cerevisiae
Gakh, O.; Obsil, T.; Adamec, J.; Spizek, J.; Amler, E.; Janata, J.; Kalousek, F.
Substrate binding changes conformation of the alpha-, but not the beta-subunit of mitochondrial processing peptidase
Arch. Biochem. Biophys.
385
392-396
2001
Saccharomyces cerevisiae
Braun, H.P.; Schmitz, U.K.
The mitochondrial processing peptidase
Int. J. Biochem. Cell Biol.
29
1043-1045
1997
Neurospora sp., Rattus norvegicus, Saccharomyces cerevisiae, Solanum tuberosum, Triticum aestivum
Shimokata, K.; Kitada, S.; Ogishima, T.; Ito, A.
Role of alpha-subunit of mitochondrial processing peptidase in substrate recognition
J. Biol. Chem.
273
25158-25163
1998
Saccharomyces cerevisiae
Kojima, K.; Kitada, S.; Shimokata, K.; Ogishima, T.; Ito, A.
Cooperative formation of a substrate binding pocket by alpha- and beta-subunits of mitochondrial processing peptidase
J. Biol. Chem.
273
32542-32546
1998
Saccharomyces cerevisiae
Kitada, S.; Kojima, K.; Shimokata, K.; Ogishima, T.; Ito, A.
Glutamate residues required for substrate binding and cleavage activity in mitochondrial processing peptidase
J. Biol. Chem.
273
32547-32553
1998
Saccharomyces cerevisiae, Rattus norvegicus
Kojima, K.; Kitada, S.; Ogishima, T.; Ito, A.
A proposed common structure of substrates bound to mitochondrial processing peptidase
J. Biol. Chem.
276
2115-2121
2001
Saccharomyces cerevisiae
Kitada, S.; Yamasaki, E.; Kojima, K.; Ito, A.
Determination of the cleavage site of the presequence by mitochondrial processing peptidase on the substrate binding scaffold and the multiple subsites inside a molecular cavity
J. Biol. Chem.
278
1879-1885
2003
Saccharomyces cerevisiae, Rattus norvegicus
Taylor, A.B.; Smith, B.S.; Kitada, S.; Kojima, K.; Miyaura, H.; Otwinowski, Z.; Ito, A.; Deisenhofer, J.
Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences
Structure
9
615-625
2001
Saccharomyces cerevisiae
Janata, J.; Hola, K.; Kubala, M.; Gakh, O.; Parkhomenko, N.; Matuskova, A.; Kutejova, E.; Amler, E.
Substrate evokes translocation of both domains in the mitochondrial processing peptidase alpha-subunit during which the C-terminus acts as a stabilizing element
Biochem. Biophys. Res. Commun.
316
211-217
2004
Saccharomyces cerevisiae
Oshima, T.; Yamasaki, E.; Ogishima, T.; Kadowaki, K.; Ito, A.; Kitada, S.
Recognition and processing of a nuclear-encoded polyprotein precursor by mitochondrial processing peptidase
Biochem. J.
385
755-761
2005
Saccharomyces cerevisiae
Murcha, M.W.; Elhafez, D.; Millar, A.H.; Whelan, J.
The N-terminal extension of plant mitochondrial carrier proteins is removed by two-step processing: the first cleavage is by the mitochondrial processing peptidase
J. Mol. Biol.
344
443-454
2004
Saccharomyces cerevisiae, Saccharomyces cerevisiae MY111-2, Solanum tuberosum
Nishino, T.G.; Kitano, K.; Kojima, K.; Ogishima, T.; Ito, A.; Kitada, S.
Spatial orientation of mitochondrial processing peptidase and a preprotein revealed by fluorescence resonance energy transfer
J. Biochem.
141
889-895
2007
Saccharomyces cerevisiae
Mukhopadhyay, A.; Yang, C.S.; Wei, B.; Weiner, H.
Precursor protein is readily degraded in mitochondrial matrix space if the leader is not processed by mitochondrial processing peptidase
J. Biol. Chem.
282
37266-37275
2007
Homo sapiens, Saccharomyces cerevisiae
Osman, C.; Wilmes, C.; Tatsuta, T.; Langer, T.
Prohibitins interact genetically with Atp23, a novel processing peptidase and chaperone for the F1Fo-ATP synthase
Mol. Biol. Cell
18
627-635
2007
Saccharomyces cerevisiae
Voegtle, F.N.; Wortelkamp, S.; Zahedi, R.P.; Becker, D.; Leidhold, C.; Gevaert, K.; Kellermann, J.; Voos, W.; Sickmann, A.; Pfanner, N.; Meisinger, C.
Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability
Cell
139
428-439
2009
Saccharomyces cerevisiae
Naamati, A.; Regev-Rudzki, N.; Galperin, S.; Lill, R.; Pines, O.
Dual targeting of Nfs1 and discovery of its novel processing enzyme, Icp55
J. BIOL. CHEM.
284
30200-30208
2009
Saccharomyces cerevisiae
Mossmann, D.; Meisinger, C.; Voegtle, F.
Processing of mitochondrial presequences
Biochim. Biophys. Acta
1819
1098-1106
2012
Saccharomyces cerevisiae
Burkhart, J.M.; Taskin, A.A.; Zahedi, R.P.; Voegtle, F.N.
Quantitative profiling for substrates of the mitochondrial presequence processing protease reveals a set of nonsubstrate proteins increased upon proteotoxic stress
J. Proteome Res.
14
4550-4563
2015
Saccharomyces cerevisiae (P10507 AND P11914), Saccharomyces cerevisiae ATCC 204508 (P10507 AND P11914)
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