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Enzyme Nomenclature
Information on EC 3.4.21.107 - peptidase Do
Word Map on EC 3.4.21.107
- 3.4.21.107
- degeneration
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age-related
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macular
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periplasmic
- parkinsonism
- neovascularization
- leukoencephalopathy
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misfolded
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arteriopathy
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subcortical
- maculopathy
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polypoidal
- medicine
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extracytoplasmic
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drusen
- biotechnology
- molecular biology
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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EC NUMBER 
COMMENTARY 
3.4.21.107
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RECOMMENDED NAME
GeneOntology No.
peptidase Do
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-/-Val
acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-/-Val
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acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-/-Val
the trypsin-like serine protease catalytic triad formed by His129, Asp158, and Ser240
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
cleavage of C-N-linkage
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hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
161108-11-8
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
a member of the Burkholderia cepacia complex, strains J2315 and K56-2
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653189, 669699, 683641, 683704, 683885, 707066, 710167, 710775, 710804, 710866, 711674, 712207, 712385, 712536, 712546, 712876, 713015, 713342, 717505, 717650, 718104, 718153
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mucoid strain FRD1 and nonmucoid strain PAO1, gene mucD encoded in the algT-mucABCD operon
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649410, 650414, 651398, 651613, 651615, 651624, 651710, 651849, 651878, 652313, 652808, 653189, 653253, 653255, 653262, 667253, 667757, 668667, 669100, 669278, 683076, 700046, 700942, 711436, 712109, 713496, 718153, 718280, 731794
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DegP; strain SL3261, gene degP or htrA
SwissProt
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme belongs to the HtrA protein family combines chaperone and protease activities and is essential for protein quality control in many organisms. HtrA proteins are composed of a chymotrypsin-like protease domain and one (DegS, HTRA1, HTRA2) or two PDZ domains (DegP, DegQ)
malfunction
metabolism
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one of the targets of HtrA1 activity during fetal development is the tuberous sclerosis complex 2-tuberous sclerosis complex 1 pathway
physiological function
additional information
enzyme structure analysis of the 12 and 24mer states in complex with model substrates, overview. DegQ PDZ domains are located adjacent to substrate density and their presence is required for chaperone activity
malfunction
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stable knockdown of HtrA1 in SKOV-3 and TOV-21G cells results in resistance to anoikis due to enhanced activation of epidermal growth factor receptor/AKT pathway. Downregulation of HtrA1 significantly enhances the peritoneal dissemination of SKOV-3ip1 cells in nonobese diabetic/severe combined immunodeficient mice
malfunction
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HTRA1 is involved in complement regulation and amyloid deposition in age-related macular degeneration pathogenesis
malfunction
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lack of nuclear localisation of Nma111p causes late onset of cell death during chronological ageing
malfunction
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Bordetella pertussis lacking the periplasmic chaperone/protease DegP has a strong growth defect at 37°C, and the integrity of its outer membrane is compromised
malfunction
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cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy-associated mutant HTRA1 decreases protease activity and fails to decrease transforming growth factor-beta family signaling
malfunction
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HTRA1 knockout mice display reduced blood vessel in retina and upregulation of growth differentiation factor 6
malfunction
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disruption of the high temperature requirement A gene affects significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress, exhibit delayed proliferation, and show a decrease of over six orders of magnitude in virulence as compared with the parental wild type strain
malfunction
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the loss of HTRA activity is correlated with severe diseases, including arthritis, cancer, familial ischemic cerebral smallvessel disease and age-related macular degeneration, as well as Parkinson’s disease and Alzheimer’s disease
malfunction
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disruption of the high temperature requirement A gene affects significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress, exhibit delayed proliferation, and show a decrease of over six orders of magnitude in virulence as compared with the parental wild type strain
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physiological function
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HtrA1 is involved in the inhibition of tumor growth factor-beta signaling in endometrial tissues
physiological function
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HtrA is involved in the ability of the pneumococcus to grow at high temperature, to resist oxidative stress and control the bacteriocin activity
physiological function
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HtrA1 protease activity is required for inhibition of epidermal growth factor receptor signaling
physiological function
DegP is a periplasmic heat-shock protein and a key component of protein quality control in the bacterial envelope. DegP along with the Skp chaperone functions to rescue outer membrane proteins that escape recognition by SurA. At temperatures below 28°C, DegP is able to protect misfolded proteins from forming aggregates, whereas at temperatures above 30°C, misfolded proteins are efficiently degraded by DegP
physiological function
DegP enhances the ability of TX01 to disseminate in fish blood at the advanced stage of infection, heightenes the activity of type 2 autoinducer, and increases the expression of luxS and the genes encoding components of the virulence-associated type III secretion system
physiological function
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the chaperone activity but not the protease activity of DegP is required for growth of ssrA-deficient cells at high themperature
physiological function
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HtrA1 is a critical protease involved in proteoglycan turnover and cartilage degradation during degenerative joint disease
physiological function
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Nma111p functions as a nuclear serine protease that is necessary for apoptosis under cellular stress conditions, such as elevated temperature or treatment of cells with hydrogen peroxide to induce cell death. The nuclear localisation of Nma111p is required for its function in response to oxidative stress
physiological function
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HtrA1 is implicated in trophoblast cell migration and invasion, tumor progression, chemotherapy-induced cytotoxicity, osteoarthritis, age-related macular degeneration, and pathogenesis of Alzheimer's disease
physiological function
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HtrA3 plays an important role in ovarian development, granulosa cell differentiation and luteinization
physiological function
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HtrA1 modulates microtubule stability and cell motility. In vitro, purified HtrA1 promotes microtubule assembly
physiological function
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HtrA plays an important role during acid stress in Streptococcus mutans
physiological function
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DegP is critical for growth and for membrane integrity of Bordetella pertussis at 37°C. The chaperone activity of DegP markedly alleviates the periplasmic stress, DegP chaperones the extended filamentous haemagglutinin polypeptide in the periplasm and is thus involved in the two-partner secretion pathway
physiological function
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DegP can act as a chaperone and a protease at the same time. Deg P is a key player in extracytoplasmic protein quality control and exhibits features of a protective factor during protein folding stress. As a chaperone, DegP refolds periplasmic amylase MalS and the artificial substrate citrate synthase
physiological function
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HtrA displays both temperature-dependent chaperone and protease activities. The HtrA chaperone activity is sufficient for growth at high temperature or under oxidative stress (in the presence of H2O2, cumene hydroperoxide or paraquat) whereas the HtrA protease activity is essential only under conditions close to the growth limit for Campylobacter jejuni. However, the protease activity is required to prevent induction of the cytoplasmic heat shock response even under optimal growth conditions. HtrA may protect oxidatively damaged proteins
physiological function
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HtrA, HhoA and HhoB are important for survival of Synechocystis sp. strain PCC 6803 under high light and temperature stresses. The three proteases may act as protein-quality-control factors degrading denatured and damaged proteins
physiological function
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HtrA is a secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of E-cadherin. the E-cadherin shedding disrupts epithelial barrier functions allowing Helicobacter pylori to access the intercellular space
physiological function
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HTRA1 decreases transforming growth factor-beta1 signaling triggered by pro-transforming growth factor-beta1 in the intracellular space
physiological function
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HTRA1 plays a critical role in the regulation of angiogenesis via transforming growth factor-beta signaling
physiological function
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HtrA is a major virulence determinant of Bacillus anthracis
physiological function
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HtrA acts as chaperone and protease. DEG1 interacts with the reaction centre protein D2 and assists in the assembly of photosystem II
physiological function
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HtrA acts as chaperone and protease. DEG1 interacts with the reaction centre protein D2 and assists in the assembly of photosystem II
physiological function
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isoform HTRA1 regulates cell proliferation by sequestering or proteolysing transforming growth factor-beta and bone morphogenetic protein, proteins of the transforming growth factor family, and IGF-binding protein 5 in the extracellular matrix. Isoform HTRA2 affects quality control in the intermembrane space of mitochondria. HTRA1 and HTRA2 are implicated in tumor suppression and in the control of proliferation, migration and neurodegeneration. Isoform HTRA3 is implicated in pregnancy, and endometrial and ovarian cancers55
physiological function
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HtrA is important for the biogenesis of extracellular proteins and thus for biofilm formation
physiological function
Plasmodium falciparum PfDegP complements the growth defect of the temperature sensitive DegP-deficient mutant in Escherichia coli and imparts resistance to non-permissive temperatures and oxidative stress. DegP exists as a complex with parasite-encoded heat shock protein 70, iron superoxide dismutase and enolase
physiological function
HtrA deletion mutant shows enhanced virulence in the Golden Syrian hamster model of acute Clostridium difficile infection. Deletion of HtrA shows a pleiotropic effect on the transcriptome of Clostridium difficile, including upregulation of the toxin A gene. The mutant shows reduced spore formation and adherence to colonic cells
physiological function
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HtrA mutants stimulate the blp locus which is responsible for the regulation and secretion of pneumococcal bacteriocins at lower cell density and to a greater extent than strains expressing wild-type HtrA. This effect is not due to direct proteolytic degradation of secreted pheromone by the protease, but instead is a result of HtrA-mediated disruption of peptide processing and secretion. HtrA restricts pneumocin production to high cell density by limiting the rate of accumulation of BlpC, a p eptide pheromone involved in quorum sensing, in the environment. HtrA does not interfere with the ability of a strain to sense environmental pheromones
physiological function
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HtrA deletion leads to severe defects in E-cadherin cleavage, loss of cell adherence, paracellular transmigration, and basolateral invasion. A conserved pocket in the active center exhibits pronounced proteolytic activity
physiological function
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Chlamydia trachomatis isolates with distinct replicative phase growth kinetics show significant loss of viable infectious progeny after HtrA is inhibited during the replicative phase
physiological function
enzyme is not able to complement an Escherichia coli DegP deletion mutant
physiological function
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HtrA is a major virulence determinant of Bacillus anthracis
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physiological function
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enzyme is not able to complement an Escherichia coli DegP deletion mutant
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physiological function
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HtrA displays both temperature-dependent chaperone and protease activities. The HtrA chaperone activity is sufficient for growth at high temperature or under oxidative stress (in the presence of H2O2, cumene hydroperoxide or paraquat) whereas the HtrA protease activity is essential only under conditions close to the growth limit for Campylobacter jejuni. However, the protease activity is required to prevent induction of the cytoplasmic heat shock response even under optimal growth conditions. HtrA may protect oxidatively damaged proteins
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physiological function
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HtrA deletion mutant shows enhanced virulence in the Golden Syrian hamster model of acute Clostridium difficile infection. Deletion of HtrA shows a pleiotropic effect on the transcriptome of Clostridium difficile, including upregulation of the toxin A gene. The mutant shows reduced spore formation and adherence to colonic cells
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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
aggrecan + H2O
aggrecan fragments
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the HtrA1-specific cleavage site is VQTV3562357TWPD within the interglobular domain of aggrecan
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?
citrate synthase + H2O
?
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acts on the thermally unfolded synthase but not on the native form
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?
competence-stimulating peptide CSP-1 + H2O
?
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enzyme HtrA constitutes the primary extracytoplasmic competence-stimulating peptide-degrading activity in cultures of Streptococcus pneumoniae. Both substrate isoforms CSP-1 and CSP-2 interact with HtrA with similar efficiencies
cleavage predominantly follows residue Phe8 of the CSP-1 isoform of the peptide within its central hydrophobic patch
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?
competence-stimulating peptide CSP-2 + H2O
?
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enzyme HtrA constitutes the primary extracytoplasmic competence-stimulating peptide-degrading activity in cultures of Streptococcus pneumoniae. Both substrate isoforms CSP-1 and CSP-2 interact with HtrA with similar efficiencies
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?
CSP-1 FRET peptide + H2O
?
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reporter peptide with incorporation of a QSY-7 quencher and a Cys(Alexa488) fluorophore at theN-erminus andC-terminus of CSP-1, respectively
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?
D1 protein + H2O
?
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degrades photodamaged D1 protein of photosystem II
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?
E-cadherin + H2O
85 kDa N-terminal fragment + 40 kDa C-terminal fragment
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selective substrate
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?
Faa1p + H2O
?
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direct interaction of Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis, Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity, overview
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?
filamentous haemagglutinin precursor + H2O
?
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DegP contributes to degrading the filamentous haemagglutinin precursor when it is blocked intracellularly
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?
insulin growth factor-binding protein 5 + H2O
?
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substrate of isoform HTRA1
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?
Lysozyme + H2O
?
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can only be digested in the presence of reducing agents
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?
outer membrane protein A + H2O
?
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in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
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?
outer membrane protein C + H2O
?
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in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
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?
outer membrane protein F + H2O
?
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in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
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?
pro-transforming growth factor-beta1 + H2O
mature transforming growth factor-beta1 + latency-associated peptide
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latency-associated peptide is the N-terminal of pro-transforming growth factor-beta1
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?
PVFNTLPMMGKASPV-4-nitroanilide + H2O
PVFNTLPMMGKASPV + 4-nitroaniline
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?
succinyl-Leu-Leu-Val-Tyr-4-methylcoumarin 7-amide + H2O
succinyl-Leu-Leu-Val-Tyr + 7-amino-4-methylcoumarin
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?
tuberous sclerosis complex 2 protein + H2O
?
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specific substrate for HtrA1 which is cleaved both in vitro and in vivo
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?
VFNTLPMMGKASPV-4-nitroanilide + H2O
VFNTLPMMGKASPV + 4-nitroaniline
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?
alpha-lactalbumin + H2O
?
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only when incubated in the presence of 20 mM dithiothreitol, which reduces the structural disulfide bonds and unfold the protein, and above 34°C, is CtHtrA able to proteolyse alpha-lactalbumin
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?
alpha-lactalbumin + H2O
?
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acts on the fully unfolded protein but not on the native form
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?
beta-casein + H2O
?
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cleaves beta-casein yielding several polypeptide fragments
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?
beta-casein + H2O
?
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little uncleaved beta-casein remains in assays with recombinant HtrA, and a prominent degradation fragment appears. Recombinant HhoA completely degrades the excess of beta-casein, whereas recombinant HhoB shows only little activity and generates a prominent degradation fragment with a slightly lower molecular mass than intact beta-casein. The C-terminal cleavage sites Val162, Gln141 and Val130 are identified for recombinant HtrA. A common cleavage site at Leu165 is found for HhoA and HhoB, however, HhoA additionally cleaves beta-casein at Ala101 generating two proteolytic fragments, the N-terminal 1-101 as well as the C-terminal 102-199 amino acid fragments
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-
?
beta-casein + H2O
beta-casein peptide fragments
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the cleavage activity at 37°C is ATP independent, not significantly influenced by buffer composition, active over a broad range of pH, and with a broad optimum at pH 6.5, and 20 mM salts, e.g. magnesium sulfate, magnesium chloride, or sodium chloride, improving activity, determination of cleavage sites
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?
Bovine serum albumin + H2O
?
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85% of the activity with casein
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?
chemotaxis signal transduction phosphatase CheX + H2O
?
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?
chemotaxis signal transduction phosphatase CheX + H2O
?
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?
colicin A lysis protein + H2O
?
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i.e. pCal, hydrolyses the acylated precursor form, cleaves at two sites near the C-terminal end to give two truncated proteins which are matured into two truncated Cals
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?
colicin A lysis protein + H2O
?
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i.e. pCal, hydrolyses the acylated precursor form, cleaves at two sites near the C-terminal end to give two truncated proteins which are matured into two truncated Cals
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?
decorin + H2O
decorin peptide fragments
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a small leucine-rich proteoglycan
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?
decorin + H2O
decorin peptide fragments
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the small leucine-rich proteoglycan is highly expressed in bone and regulates type I collagen fibril assembly
generation of fragments ranging from 150 to 75 kDa
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?
decorin + H2O
decorin peptide fragments
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a small leucine-rich proteoglycan, human substrate
generation of fragments ranging from 150 to 75 kDa
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?
E-cadherin + H2O
?
enzyme cleaves E-cadherin on host cells
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?
fibronectin + H2O
fibronectin peptide fragments
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HtrA is involved in cartilage catabolism
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?
fibronectin + H2O
fibronectin peptide fragments
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a major noncollagenous component of mineralized bone matrix
generation of fragments ranging from 200 to 150 kDa
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?
fibronectin + H2O
fibronectin peptide fragments
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human plasma-derived substrate
generation of fragments ranging from 200 to 150 kDa
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?
FkpA + H2O
?
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periplasmic peptidyl-prolyl cis–trans isomerase, chaperone
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-
?
FkpA + H2O
?
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periplasmic peptidyl-prolyl cis-trans isomerase, chaperone
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-
?
insulin beta-chain + H2O
?
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oxidized beta-chain which is fully unfolded
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?
malate dehydrogenase + H2O
?
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acts on the thermally unfolded protein but not on the native form
-
?
matrix Gla protein + H2O
processed matrix Gla protein + 12 kDa peptide
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the protein substrate is present in cartilage, bone, and arteries
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-
?
matrix Gla protein + H2O
processed matrix Gla protein + 12 kDa peptide
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cleavage of MGP at the C terminus
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-
?
N-acetyl-L-tyrosine ethyl ester + H2O
N-acetyl-L-tyrosine + ethanol
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51% of the activity with casein
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-
?
N-acetyl-L-tyrosine ethyl ester + H2O
N-acetyl-L-tyrosine + ethanol
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51% of the activity with casein
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-
?
Protein + H2O
?
-
cleaves model substrates at discrete Val/Xaa or Ile/Xaa sites
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?
Protein + H2O
?
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cleaves preferably at hydrophobic side chains at the P1 position
-
?
Protein + H2O
?
-
denatured proteins aggregate to form a distinct S fraction, one third of the isolated S fraction is converted to trichloroacetic acid-soluble products
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?
Protein + H2O
?
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denatured proteins aggregate to form a distinct S fraction, one third of the isolated S fraction is converted to trichloroacetic acid-soluble products, enzyme has a preference for valine or isoleucine as the residue preceding the cleavage site
-
?
Protein + H2O
?
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enzyme recognizes an ssrA-encoded peptide tag which is tagged to misfolded proteins or protein fragments
-
?
reaction centre protein D2 + H2O
?
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
reaction centre protein D2 + H2O
?
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
the enzyme plays a role in the Burkholderia cenocepacia stress response, HtrABCAL2829 is required for growth of Burkholderia cenocepacia upon exposure to osmotic stress by NaCl or KCl, and thermal stress at 44°C
-
-
-
additional information
?
-
-
HtrA sequence specificity, overview, no activity with albumin and myoglobin at 37°C, HtrA acts as both a chaperone and protease, HtrA mutant S247A is able to chaperone insulin B-chain, irrespective of temperature, but at 30°C only HtrA and not mutant S247A displays significant chaperone activity for alpha-lactalbumin, overview
-
-
-
additional information
?
-
-
acts on substrates that are at least partially unfolded, does not cleave stably folded proteins, acts as a general chaperone forming stable complexes with several misfolded proteins
-
?
additional information
?
-
-
no substrates are: bovine serum albumin, ovalbumin, globin, insulin and other peptides that are routinely used as protease substrates
-
?
additional information
?
-
-
no substrates are: native bovine serum albumin, insulin, growth hormone or a variety of commonly used peptide substrates
-
?
additional information
?
-
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heat shock serine protease that degrades misfolded proteins at high temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at elevated temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, participate in removal of aggregated proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, switches from chaperone to protease function in a temperature-dependent manner
-
?
additional information
?
-
-
involved in the degradation of denatured and unfolded proteins
-
?
additional information
?
-
-
involved in the degradation of misfolded proteins
-
?
additional information
?
-
-
involved in the degradation of unfolded proteins
-
?
additional information
?
-
-
unable to cleave inhibitor of apoptosis protein
-
-
-
additional information
?
-
-
allosteric activation of DegP by stress signals during bacterial protein quality control, regulation mechanism, pathway scheme, overview
-
-
-
additional information
?
-
-
HtrA inhibits the unfolded lysozyme substrate aggregation over the range of temperatures at 30-45°C, HtrA is able to bind to the denatured polypeptides and as a consequence limits their ability to form large aggregates, overview, HtrA may protect the bacterial cells from deleterious effects of heat shock not only by degrading the damaged proteins but by combination of the proteolytic and chaperoning activities
-
-
-
additional information
?
-
-
HtrA shows chaperone-like activity, overview
-
-
-
additional information
?
-
-
when unfolded proteins bind to CpxP, DegP efficiently degrades this protein complex
-
-
-
additional information
?
-
-
almost no activity towards SDAEFRHDSGYEV-4-nitroanilide, SDAEFRHDSGYEV-4-nitroanilide, SGRVVPGYGHA-4-nitroanilide, SPLPEGV-4-nitroanilide , GLATGNVSTAELQDATPA-4-nitroanilide, KGKNSGSGATPV-4-nitroanilide, KGASVPGAGLV-4-nitroanilide, SPAKGGEEPLPEGV-4-nitroanilide, and benzoyl-L-Arg-4-nitroanilide
-
-
-
additional information
?
-
-
identification of beta-barrel outer membrane proteins, OMPs, as major natural substrates by photo-crosslinking using non-natural amino acid DiZPK, 3-(3-methyl-3H-diazirine-3-yl)-propaminocarbonyl-Nepsilon-L-lysine, as the photo-crosslinker. Isoform DegP primarily functions as a protease, at both low and high temperatures, to eliminate unfolded outer membrane proteins, with hardly any appreciable chaperone activity in cells. The toxic and cell membrane-damaging misfolded outer membrane proteins would accumulate in DegP-lacking cells cultured under heat shock conditions
-
-
-
additional information
?
-
the enzyme shows chaperone-like activity with substrate lysozyme, and protease activity. The PDZ domains are needed for DegQ chaperone activity. Up to six lysozyme substrates bind inside the DegQ dodecamer cage, binding of a well-ordered lysozyme to four DegQ protomers, overview
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
the enzyme does not cleave recombinant immunoglobulin A, epidermal growth factor receptor or junctional adhesion molecule
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins, involved in arthritis, cell growth, stress response, apoptosis and aging, possible tumor suppressor function
-
?
additional information
?
-
-
HtrA1 expression is regulated by cisplatin and paclitaxel, and upregulation results in catalytic activation of HtrA1, overview, HtrA1 influences tumor response to chemotherapy by modulating hemotherapy-induced cytotoxicity, HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance, overview
-
-
-
additional information
?
-
-
HtrA1 plays a role in arthritic disease, within the context of arthritis pathology HtrA1 contributes to cartilage degradation, overview
-
-
-
additional information
?
-
-
HTRA1 does not cleave CFH protein, complement component C3 and complement component C3b
-
-
-
additional information
?
-
-
HTRA1 interacts with presenilin 1 to cleave one product of gamma-secretase
-
-
-
additional information
?
-
-
HTRA1 fails to cleave mature transforming growth factor-beta1
-
-
-
additional information
?
-
-
HtrA1 shows no activity towards tuberous sclerosis complex 1 protein and bovine serum albumin
-
-
-
additional information
?
-
role in extracellular proteolysis, proteolysis occurs during or after export to the cell surface, involved in the degradation of abnormal exported proteins
-
?
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins, acts as protease, chaperone and regulator of apoptosis
-
?
additional information
?
-
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
-
HtrA1 degrades specific matrix-associated proteins, HtrA1 inhibits mineral deposition by osteoblasts, the protease domain and the PDZ domain are essential for the inhibition of osteoblast mineralization by HtrA1, overview
-
-
-
additional information
?
-
-
HtrA1 is a secreted multidomain protein with serine protease activity
-
-
-
additional information
?
-
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
-
MucD negatively regulates alginate production on genetic level, MucD-deficient strain show temperature-dependent alginate production, while MucD-containing strains do not, which is independent of MucD proteolytic activity, overview
-
-
-
additional information
?
-
-
DegP degrades unfolded or misfolded, secreted, and accumulated inactive proteins and is important for cell survival, especially in the absence of DsbA
-
-
-
additional information
?
-
-
mutants are deficient in their ability to survive in mice or macrophages
-
?
additional information
?
-
the enzyme is involved in survival of the bacteria under heat shock stress conditions in vitro and in vivo, overview
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
enzyme displays a preference for substrates with non-polar residues at the P1 site
-
-
-
additional information
?
-
-
HtrA is essential for the maturation of cysteine protease streptococcal pyrogenic exotoxin B, SpeB, but is unable to directly process SpeB zymogen, proSpeB to the active form in vitro, thus playing an indirect role in the maturation, overview
-
-
-
additional information
?
-
-
no activity with correctly folded globular bovine serum albumin or lysozyme
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, chaperone and proteolytic activity
-
?
additional information
?
-
HtrA1 promotes posterior development in mRNA-injected Xenopus laevis embryos, e.g. induces secondary tail-like structures, expansion of mesoderm, and formation of ectopic neurons in an FGF-dependent manner, HtrA1 activates FGF/ERK signaling and the transcription of FGF genes by cleaving proteoglycans and releasing cell surface-bound FGF ligands, overview
-
-
-
additional information
?
-
-
deletion mutant is unable to grow at an elevated temperature and to survive within macrophages after phagocytosis
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
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
aggrecan + H2O
aggrecan fragments
-
the HtrA1-specific cleavage site is VQTV3562357TWPD within the interglobular domain of aggrecan
-
-
?
decorin + H2O
decorin peptide fragments
-
the small leucine-rich proteoglycan is highly expressed in bone and regulates type I collagen fibril assembly
generation of fragments ranging from 150 to 75 kDa
-
?
E-cadherin + H2O
85 kDa N-terminal fragment + 40 kDa C-terminal fragment
-
selective substrate
-
-
?
Faa1p + H2O
?
-
direct interaction of Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis, Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity, overview
-
-
?
filamentous haemagglutinin precursor + H2O
?
-
DegP contributes to degrading the filamentous haemagglutinin precursor when it is blocked intracellularly
-
-
?
FkpA + H2O
?
-
periplasmic peptidyl-prolyl cis–trans isomerase, chaperone
-
-
?
insulin growth factor-binding protein 5 + H2O
?
-
substrate of isoform HTRA1
-
-
?
matrix Gla protein + H2O
processed matrix Gla protein + 12 kDa peptide
-
the protein substrate is present in cartilage, bone, and arteries
-
-
?
outer membrane protein A + H2O
?
-
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
outer membrane protein C + H2O
?
-
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
outer membrane protein F + H2O
?
-
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
tuberous sclerosis complex 2 protein + H2O
?
-
specific substrate for HtrA1 which is cleaved both in vitro and in vivo
-
-
?
fibronectin + H2O
fibronectin peptide fragments
-
HtrA is involved in cartilage catabolism
-
-
?
fibronectin + H2O
fibronectin peptide fragments
-
a major noncollagenous component of mineralized bone matrix
generation of fragments ranging from 200 to 150 kDa
-
?
reaction centre protein D2 + H2O
?
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
reaction centre protein D2 + H2O
?
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
the enzyme plays a role in the Burkholderia cenocepacia stress response, HtrABCAL2829 is required for growth of Burkholderia cenocepacia upon exposure to osmotic stress by NaCl or KCl, and thermal stress at 44°C
-
-
-
additional information
?
-
-
heat shock serine protease that degrades misfolded proteins at high temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
P0C0V0
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at elevated temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, participate in removal of aggregated proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, switches from chaperone to protease function in a temperature-dependent manner
-
?
additional information
?
-
-
involved in the degradation of denatured and unfolded proteins
-
?
additional information
?
-
-
involved in the degradation of misfolded proteins
-
?
additional information
?
-
-
involved in the degradation of unfolded proteins
-
?
additional information
?
-
-
allosteric activation of DegP by stress signals during bacterial protein quality control, regulation mechanism, pathway scheme, overview
-
-
-
additional information
?
-
-
HtrA inhibits the unfolded lysozyme substrate aggregation over the range of temperatures at 30-45°C, HtrA is able to bind to the denatured polypeptides and as a consequence limits their ability to form large aggregates, overview, HtrA may protect the bacterial cells from deleterious effects of heat shock not only by degrading the damaged proteins but by combination of the proteolytic and chaperoning activities
-
-
-
additional information
?
-
-
when unfolded proteins bind to CpxP, DegP efficiently degrades this protein complex
-
-
-
additional information
?
-
-
identification of beta-barrel outer membrane proteins, OMPs, as major natural substrates by photo-crosslinking using non-natural amino acid DiZPK, 3-(3-methyl-3H-diazirine-3-yl)-propaminocarbonyl-Nepsilon-L-lysine, as the photo-crosslinker. Isoform DegP primarily functions as a protease, at both low and high temperatures, to eliminate unfolded outer membrane proteins, with hardly any appreciable chaperone activity in cells. The toxic and cell membrane-damaging misfolded outer membrane proteins would accumulate in DegP-lacking cells cultured under heat shock conditions
-
-
-
additional information
?
-
P39099
the enzyme shows chaperone-like activity with substrate lysozyme, and protease activity. The PDZ domains are needed for DegQ chaperone activity. Up to six lysozyme substrates bind inside the DegQ dodecamer cage, binding of a well-ordered lysozyme to four DegQ protomers, overview
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, involved in arthritis, cell growth, stress response, apoptosis and aging, possible tumor suppressor function
-
?
additional information
?
-
-
HtrA1 expression is regulated by cisplatin and paclitaxel, and upregulation results in catalytic activation of HtrA1, overview, HtrA1 influences tumor response to chemotherapy by modulating hemotherapy-induced cytotoxicity, HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance, overview
-
-
-
additional information
?
-
-
HtrA1 plays a role in arthritic disease, within the context of arthritis pathology HtrA1 contributes to cartilage degradation, overview
-
-
-
additional information
?
-
-
HTRA1 does not cleave CFH protein, complement component C3 and complement component C3b
-
-
-
additional information
?
-
-
HTRA1 interacts with presenilin 1 to cleave one product of gamma-secretase
-
-
-
additional information
?
-
Q9LA06
role in extracellular proteolysis, proteolysis occurs during or after export to the cell surface, involved in the degradation of abnormal exported proteins
-
?
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins, acts as protease, chaperone and regulator of apoptosis
-
?
additional information
?
-
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
-
HtrA1 degrades specific matrix-associated proteins, HtrA1 inhibits mineral deposition by osteoblasts, the protease domain and the PDZ domain are essential for the inhibition of osteoblast mineralization by HtrA1, overview
-
-
-
additional information
?
-
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
-
MucD negatively regulates alginate production on genetic level, MucD-deficient strain show temperature-dependent alginate production, while MucD-containing strains do not, which is independent of MucD proteolytic activity, overview
-
-
-
additional information
?
-
-
DegP degrades unfolded or misfolded, secreted, and accumulated inactive proteins and is important for cell survival, especially in the absence of DsbA
-
-
-
additional information
?
-
-
mutants are deficient in their ability to survive in mice or macrophages
-
?
additional information
?
-
P26982
the enzyme is involved in survival of the bacteria under heat shock stress conditions in vitro and in vivo, overview
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
HtrA is essential for the maturation of cysteine protease streptococcal pyrogenic exotoxin B, SpeB, but is unable to directly process SpeB zymogen, proSpeB to the active form in vitro, thus playing an indirect role in the maturation, overview
-
-
-
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, chaperone and proteolytic activity
-
?
additional information
?
-
A6YFB5
HtrA1 promotes posterior development in mRNA-injected Xenopus laevis embryos, e.g. induces secondary tail-like structures, expansion of mesoderm, and formation of ectopic neurons in an FGF-dependent manner, HtrA1 activates FGF/ERK signaling and the transcription of FGF genes by cleaving proteoglycans and releasing cell surface-bound FGF ligands, overview
-
-
-
additional information
?
-
-
deletion mutant is unable to grow at an elevated temperature and to survive within macrophages after phagocytosis
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
MgCl2
NaCl
Ca2+
-
the activity of recombinant HtrA and HhoA increases almost 4-6fold in the presence of 5 mM CaCl2 and remains constant at higher concentrations. The activity of recombinant HhoB increases more gradually up to 14fold, reaching the maximal level at 10 mM CaCl2. Almost no proteolytic activity is detected for recombinant HhoB in the absence of Ca2+
Mg2+
-
the activity of recombinant HtrA and HhoA increases almost 4-6fold in the presence of 5 mM MgCl2 and remains constant at higher concentrations. The activity of recombinant HhoB increases more gradually up to 14fold, reaching the maximal level at 10 mM MgCl2
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
HpHtrA inhibitor
-
small-molecule inhibitor that completely blocks E-cadherin cleavage by HtrA at 0.03 mM
-
N-(tert-butoxycarbonyl)-L-valyl-N-[(1R)-1-(diphenoxyphosphoryl)-2-methylpropyl]prolinamide
N-(tert-butoxycarbonyl)-L-valyl-N-[(1R)-1-(diphenoxyphosphoryl)-2-methylpropyl]prolinamide
-
i.e. JO146. Inhibition during the replicative phase results in significant loss of viable infectious progeny
N-(tert-butoxycarbonyl)-L-valyl-N-[(1R)-1-(diphenoxyphosphoryl)-2-methylpropyl]prolinamide
-
i.e. JO146. Inhibition during the replicative phase results in significant loss of viable infectious progeny
N-(tert-butoxycarbonyl)-L-valyl-N-[(1R)-1-(diphenoxyphosphoryl)-2-methylpropyl]prolinamide
-
i.e. JO146. Inhibition during the replicative phase results in significant loss of viable infectious progeny
additional information
-
wild type and HtrA mutant are not sensitive to H2O2, cumene hydroperoxide and paraquat, moreover the wild type is not sensitive to oxygen while the mutant has a reduced oxygen tolerance
-
additional information
-
no inhibition by aprotinin and trypsin inhibitor
-
additional information
-
not inhibited by SGRVVPGYGHA-chloromethylketone and IWNTLNSGRVVPGTGHA-chloromethylketone
-
additional information
-
no inhibition by Z-VAD-FMK, a broad-spectrum caspase inhibitor, nor dominant-negative caspase 9
-
additional information
-
not inhibited by benzyloxycarbonyl-VAD-fluoromethylketone
-
additional information
not inhibitory: dithiothreitol, phenylmethanesulfonyl fluoride, leupeptin, E-64 and pepstatin
-
additional information
-
rHtrA-mediated decline in transformation efficiency can not be corrected with excess competence-stimulating peptide
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cardiolipin
enhances DegP proteolytic activity at high temperatures
CPII
-
cleavage of aggrecan by HtrA1 is strongly enhanced by HtrA1 agonists such as CPII, a C-terminal hexapeptide derived from the C-propeptide of procollagen IIalpha1
-
DTT
-
only when incubated in the presence of 20 mM dithiothreitol, which reduces the structural disulfide bonds and unfold the protein, and above 34°C, is CtHtrA able to proteolyse alpha-lactalbumin
OMP C-terminal tripeptide YYF-COOH
-
activation less efficient as compared to 15 residue presenilin-1 peptide
phosphatidyl glycerol
enhances DegP proteolytic activity at high temperatures
puromycin
-
increases level of misfolded proteins, HtrA is required for growth under conditions in which misfolded proteins accumulate
additional information
-
largely indpependent of activating compounds such as reducing agents
-
additional information
-
low osmolarity conditions result in HtrA repression together with the nucleoid associated proteins H-NS and HhA
-
additional information
-
allosteric activation of DegP by stress signals during bacterial protein quality control, DegP activation is based on an interaction of the activating peptide with PDZ domains
-
additional information
-
both cisplatin and paclitaxel treatment upregulates HtrA1 expression resulting in limited autoproteolysis and activation of HtrA1, active HtrA1 induces cell death in a serine protease-dependent manner and activates caspase-3/7 activity, overview
-
additional information
DegP and DegQ are constitutive, while DegS needs to be activated by an extracellular signal
-
additional information
HtrA1 is expressed in early embryo and activated by FGF signals
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0346
succinyl-Leu-Leu-Val-Tyr-4-methylcoumarin 7-amide
pH 7.0, temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.001
-
using PMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
0.018
-
using PVFNTLPMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication; using SPMFKGV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
0.032
-
using VFNTLPMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
0.473
-
using DPMFKLV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
additional information
-
DegP protease exhibits a concentration effect: an 8fold increase in the concentration of DegP results in an 2.4fold increase in the specific protease activity
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 6.5
-
HhoB activity shows an optimum at pH 5.5-6.5 in the presence of 10 mM Ca2+
6.5
8
-
HhoA activity shows an optimum at pH 8.0 or higher in the presence of 10 mM Ca2+
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
-
reduced alkaline phosphatase is efficiently degraded at 20°C, both in vivo and in vitro. The cleavage is most efficient in the case of a C57A/C69A mutant, lacking its internal S–S bond
37
45
50
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 30
-
almost no activity below 20°C, activity rapidly increases above 30°C
37 - 44
-
the HtrA mutant forms colonies with the same frequency as the wild type at 37°C and 42°C, the ability of the mutant to form colonies at 44°C was greatly reduced as compared to the wild type
37 - 45
44
-
at 44 °C function of DegP in mutant strain CLC198 can be complemented by HtrA2
37 - 45
-
no change of cell density of wild type, cell density of the mutant rapidly falls, protease Do essential for the cell's survival at high temperatures
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
high level of enzyme expression in decidua capsularis specifically at the decidual-trophoblast interface where active involution occurs
-
the luteinizing granulosa cells of the corpus luteum express the highest levels of Htra3
-
elevated synovial HtrA1 levels in fluids obtained from rheumatoid and osteoarthritis patients
-
HtrA1 especially expressed in giant cells during the early stages of placental development
additional information
-
from cord blood, expression and enzyme content analysis, the enzyme is constitutively released from mast cells, overview
-
peritoneal, mucosal, and connective tissue-derived mast cells, the enzyme expression is highly up-regulated during mucosal mast cell differentiation, enzyme levels in mucosal mast cells are much higher compared to connective-tissue-type mast cells, expression and enzyme content analysis, overview
-
peritoneal, mucosal, and connective tissue-derived mast cells, the enzyme expression is highly up-regulated during mucosal mast cell differentiation, enzyme levels in mucosal mast cells are much higher compared to connective-tissue-type mast cells, expression and enzyme content analysis, overview
-
additional information
-
HtrA expression can be lowered by the suppression of the acid tolerance response (ATR)
additional information
maximum transcription is observed in trophozoite- and schizont-stage parasites, with no detectable transcription observed at the ring stage
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
Nma111p does not shuttle between the nucleus and cytoplasm
-
especially close to microvilli that characterizes the plasma membrane of syncytiotrophoblast cells, or in the extracytoplasmic space of the stroma of placental villi between the collagen fibers and on collagen fibers themselves
-
constitutive secretion from mast cells unaffected by degranulating compounds
-
-
bowl-shaped DegP assemblies on membranes have higher proteolytic activity but lower chaperone-Like activity
-
HtrA1 is localized to microtubules in both interphase and mitotic cells
-
intracellular HtrA1 associates with newly polymerized microtubules
-
the N-terminal leader of the HtrA protease is required for export to the periplasmic space
-
-
-
-
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PDB
SCOP
CATH
ORGANISM
UNIPROT
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42000
44835
12 * 44835, mass spectrometry; 24 * 44835, mass spectrometry; 6 * 44835, mass spectrometry
50000
54000
-
10 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer; 5 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer; 6 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
300000
50000
-
12 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible; 6 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decamer
-
10 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
dodecamer
hexamer
homooligomer
DegP of Escherichia coli assembles into large homooligomers with an internal cavity combining both chaperone and protease activity
multimer
oligomer
pentamer
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5 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
tetracosamer
trimer
additional information
dodecamer
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12 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
dodecamer
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consists of two stacks of hexameric rings, SDS-PAGE, cross-linking experiments
hexamer
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6 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
hexamer
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6 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
hexamer
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crystal structures suggest that HtrA proteins differ in their molecular architecture, ranging from trimers with surface-accessible active sites to hexamers
hexamer
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purified wild type DegP exists mainly as hexamers (dimers of trimers) in solution
hexamer
DegP, dimer of two trimers
multimer
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gel filtration shows three DegP oligomers, namely the 6-mer (DegP6), the 12-mer (DegP12) and the 24-mer (DegP24), of which the two larger particles had additional proteins bound. Binding of misfolded proteins transforms hexameric DegP into large, catalytically active 12-meric and 24-meric multimers. A structural analysis of these particles reveal that DegP represents a protein packaging device whose central compartment is adaptable to the size and concentration of substrate. Moreover, the inner cavity serves antagonistic functions
multimer
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DegP activates its chaperone and protease functions via formation of large cage-like 12- and 24-mers after binding to substrate proteins. Cryo-electron microscopic and biochemical studies reveal that both oligomers are consistently assembled by blocks of DegP trimers, via pairwise PDZ1-PDZ2 interactions between neighboring trimers. Such interactions simultaneously eliminate the inhibitory effects of the PDZ2 domain. Additionally, both DegP oligomers are also observed in extracts of Escherichia. coli cells, strongly implicating their physiological importance
oligomer
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largest complexes are dodecamers, probably formed by dimerization of trimers, gel filtration experiments
oligomer
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DegP protease chaperone system is regulated by oligomer conversion from the resting hexamer into the catalytically active 12mer and 24mer that capture and digest misfolded proteins
oligomer
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x * about 50000, SDS-PAGE. In the absence of substrate, DegP oligomerizes as a hexameric cage but in its presence DegP reorganizes into active 12- and 24-mer cages. The size of the substrate molecule is the main factor conditioning the oligomeric state adopted by the enzyme, while ther factors such as temperature, do not influence the oligomeric state
trimer
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crystal structures suggest that HtrA proteins differ in their molecular architecture, ranging from trimers with surface-accessible active sites to hexamers
additional information
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secondary structures for activated protease at different temperatures
additional information
DegQ changes its oligomeric state from hexamers to either 12 or 24mers depending on the concentration of unfolded substrate, DegQ forms 12mers in the absence of substrate at acidic pH, enzyme structure analysis of the 12 and 24mer states in complex with model substrates, overview. The polypeptides are probably cooperatively bound by PDZ1 and protease domains
additional information
the Deg protein contain a catalytic domain with the serine protease catalytic triad, and C-terminal PDZ domains, two in DegP and DegQ, one in DegS
additional information
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HtrA contains a putative N-terminal membrane anchor domain, Ile13 to Ile26, a trypsin-like serine protease catalytic triad formed by His129, Asp158, and Ser240, and a single C-terminal PDZ domain, Gly296 to Arg385
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
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enzyme is derived by cleavage of the first 26 amino acids of the pre-HtrA precursor polypeptide
proteolytic modification
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HtrA1 activation by limited autoproteolysis, not of mutant S328A
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
mutant S266A, to 2.6 A resolution. The protein trimer contains two calcium ions in a central channel, suggesting a link between photodamage control and calcium ions in chloroplasts. Protein contains no PDZ domain and the trimeric structure reveals a catalytic triad conformation where His147 in the alternative conformation is rotated anticlockwise by 120°, preventing formation of the His147-Asp188 hydrogen bond; mutant S292A, to 2.0 A resolution. Isoform Deg8 forms a hexamer in the crystals. The catalytic triad of Deg8 consists of His171, Asp214 and Ser292. In the Deg8 (S292A) structure the triad fails to form catalytically competent hydrogen bonds owing to the anticlockwise rotation of the chi1 angle of His171 by 120°. His171 can form a hydrogen bond to Gln272 of loop L3
a theoretical model of the three-dimensional structure of the LA loop as per the resting state of enzyme HtrA. hydrophobic interactions connect the LA loops of the hexamer and polar contacts between the LA', i.e. the LA loop on an opposite subunit, and L1 loops on opposite subunits. Disturbance of these interactions causes the stimulation of HtrA proteolytic activity. LA loops contribute to the preservation of the integrity of the HtrA oligomer and to the stability of the monomer
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crystal structure of the DegP24 multimer-outer membrane protein complex is solved by the single-wavelength anomalous dispersion method: The 24-mer of DegP forms a spherical shell with 432 symmetry. In the crystal structure of DegP24, eight trimers are located at the vertices of an octahedron that assembles a protein shell of about 31 A thickness enclosing a large internal cavity about 110 A in diameter
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structure determination and analysis of the 24meric enzyme with complexed substrate beta-casein, cryo-electron microscopy images and three-dimensional structures, overview