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Information on EC 3.4.21.47 - alternative-complement-pathway C3/C5 convertase
for references in articles please use BRENDA:EC3.4.21.47
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.21 Serine endopeptidases
3.4.21.47 alternative-complement-pathway C3/C5 convertase
IUBMB Comments
A bimolecular complex of complement fragment Bb with either C3b or cobra venom factor; Bb contains the active site. Bb is formed by cleavage of proenzyme factor B by factor D. Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb complex. C3b,Bb is stabilized in plasma by factor P. Complement factor B is in peptidase family S1 (trypsin family)
The enzyme appears in viruses and cellular organisms
- 3.4.21.47
-
hemolytic
- igg
- glomerulonephritis
- erythrocyte
-
nephritic
- autoantibody
-
membranoproliferative
-
complement-mediated
-
c3nefs
-
decay-accelerating
-
cell-bound
-
opsonization
-
fluid-phase
- zymosan
- allotypes
-
uremic
- glomerulopathy
-
surface-bound
-
complement-activating
- c5b
- anaphylatoxins
- glyoxalase
-
immunofixation
- hemoglobinuria
- medicine
- eculizumab
-
hypocomplementemic
- nef
Reaction Schemes
showCleavage of Arg-/-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-/- bond in complement component C5 alpha-chain to yield C5a and C5b
Synonyms
c3bbb, c5 convertase, properdin factor b, alternative pathway c3 convertase, c3b,bb, heat-labile factor, c3/c5 convertase, c3 proactivator, cvf,bb, ap c3 convertase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(C3b)n,Bb
-
-
-
-
(CVF)-dependent glycine-rich-beta-glucoprotein
-
-
-
-
alternative complement pathway C3(C5) convertase
-
-
-
-
alternative pathway C3 convertase
alternative pathway C3-convertase
alternative-complement-pathway C3/C5 convertase
C3 convertase
C3 proactivator
-
-
-
-
C3/C5 convertase
C3b,Bb
C3bBb
C3bBb convertase
C3bBbC3b
C5 convertase
cobra venom factor-dependent C3 convertase
-
-
-
-
complement C 3(C 5) convertase (amplification)
-
-
-
-
complement component C3/C5 convertase (alternative)
-
-
-
-
convertase, complement C3(C5) (amplification)
-
-
-
-
CVF,Bb
-
-
-
-
GBG
-
-
-
-
Glycine-rich beta glycoprotein
-
-
-
-
heat-labile factor
-
-
-
-
PBF2
-
-
-
-
proenzyme factor B
-
-
-
-
properdin factor B
-
-
-
-
C3 convertase
-
-
-
-
C3 convertase
-
C3/C5 convertase
-
-
-
-
C3b,Bb
-
-
-
-
C5 convertase
-
-
-
-
C5 convertase
-
binding of an additional C3b molecule to the C3 convertase forms the C5 convertase (C3bBbC3b) of the alternative pathway
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cleavage of Arg-/-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-/- bond in complement component C5 alpha-chain to yield C5a and C5b
Cleavage of Arg-/-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-/- bond in complement component C5 alpha-chain to yield C5a and C5b
the enzyme is a bimolecular complex of complement fragment Bb with either C3b or cobra venom factor. Bb contains the active site. Bb is formed by cleavage of proenzyme factor B by factor D. Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb complex, , intermediate catalytic mechanism and a kinetic mechanism of a tetra uni ping pong bi bi reaction reduced to a uni bi reaction
-
Cleavage of Arg-/-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-/- bond in complement component C5 alpha-chain to yield C5a and C5b
factor B binding to C3b forms an open activation state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells
Cleavage of Arg-/-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-/- bond in complement component C5 alpha-chain to yield C5a and C5b
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
endopeptidase
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CAS REGISTRY NUMBER
COMMENTARY
80295-67-6
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
C2 fragment + H2O
?
-
Substrates: C-terminal fragment originating from the processing of meningococcal proteases
Products: -
Products: -
?
neisserial heparin binding antigen + H2O
?
-
Substrates: also known as GNA2132 (genome-derived Neisseria antigen 2132)
Products: -
Products: -
?
t-butyloxycarbonyl-Gly-L-Leu-L-Ala-L-Arg-thiobenzyl ester
?
Substrates: substrate of enzyme subunit Bb
Products: -
Products: -
?
tert-butoxycarbonyl-Leu-Gly-Arg-7-amido-4-methylcoumarin + H2O
tert-butoxycarbonyl-Leu-Gly-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
tert-butoxycarbonyl-norleucine-Gln-Leu-Gly-Arg-7-amido-4-methylcoumarin + H2O
tert-butoxycarbonyl-norleucine-Gln-Leu-Gly-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
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Substrates: hydrolysis of peptide bond 77 Arg-Ser of the a-chain
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
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Substrates: complement component C3 is the preferred substrate. Cleavage of the preferred C3 substrate and deposition of C3b effectively switches the output of the enzyme from C3b to C5b, resulting in initiation of the cytosolic process of complement
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: properdin-deficient patients susceptible to lethal meningococcal infection, studies on yet unknown mechanism of selective predisposition
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: cleavage of complement component C3 mediated through the MBL pathway in human serum analyzed, mannan-binding lectin (MBL) promotes activation of C3, combined action of MBL-associated serine proteases MASP-1 and MASP-2 required, involvement of the alternative pathway not detected
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: interaction studies with decay-accelerating factor DAF mediating decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme C3bB
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: studies on fluid-phase formation of initial convertase by fluorescence resonance energy transfer (FRET)
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: potencies of the amplification loop of the alternative complement pathway summarized
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: analysis of structure and function of complement component C3b in complex with the macrophage-expressed complement receptor CRIg, CRIg shown as an inhibitor of alternative complement convertases
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: complement activation in properdin-deficient mice analyzed
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: cleavage of complement component C3 through the mannan-binding lectin pathway in mouse sera determined
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
Substrates: -
Products: -
Products: -
?
complement component C3 zymogen + H2O
complement component C3b + complement component C3a
Substrates: activation
Products: -
Products: -
?
complement component C3 zymogen + H2O
complement component C3b + complement component C3a
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
Substrates: methionine-modified enzyme has significantly lower C5-cleavage ability than that of unmodified enzyme
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
Substrates: -
Products: -
Products: -
?
complement component C5 zymogen + H2O
complement component C5b + complement component C5a
Substrates: activation
Products: -
Products: -
?
complement component C5 zymogen + H2O
complement component C5b + complement component C5a
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: fragment Bb is the catalytic subunit of the enzyme, isolated Bb is unable to cleave either C3 or C5
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme has a very short half-life. Dissociation of the two noncovalently bound subunits proceeds with a half-life of 1-3 min at 37°C under physiological conditions, and this rate increases greatly if regulatory proteins are present. Numerous decay-accelerating proteins are present in plasma and on host cells that bind to the noncatalytic subunit C3b and increase the rate at which the catalytic subunit Bb is released into the medium. Bb loses its enzymatic activity and its ability to bind to C3b upon release. Although C3b is able to rebind Bb and reform the enzyme, the interaction with most decay-accelerating factors also leads to permanent proteolytic interaction of the cell-bound subunit C3b by a fluid-phase protease Factor I. These regulatory events limit cleavage of C3, reduce release of the anaphylatoxin C3a and control the formation of more efficient C5 convertase enzymes
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in the alternative pathway of human complement
Products: -
Products: -
?
additional information
?
-
-
Substrates: the activation peptide, C5a, possesses potent spasmogenic and chemotactic activity
Products: -
Products: -
?
additional information
?
-
Substrates: early complement stimulation in trauma patients analyzed, correlation with injury severity, tissue hypoperfusion and worse clinical outcomes identified
Products: -
Products: -
?
additional information
?
-
Substrates: C3b binds uniformly to substances on the surface of Escherichia coli K12, whereas it shows a bimodal distribution on the surface of Staphylococcus aureus P209. Autoactivation activity of C3
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
C2 fragment + H2O
?
-
Substrates: C-terminal fragment originating from the processing of meningococcal proteases
Products: -
Products: -
?
complement component C3 zymogen + H2O
complement component C3b + complement component C3a
Substrates: activation
Products: -
Products: -
?
complement component C5 zymogen + H2O
complement component C5b + complement component C5a
Substrates: activation
Products: -
Products: -
?
neisserial heparin binding antigen + H2O
?
-
Substrates: also known as GNA2132 (genome-derived Neisseria antigen 2132)
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
Substrates: complement component C3 is the preferred substrate. Cleavage of the preferred C3 substrate and deposition of C3b effectively switches the output of the enzyme from C3b to C5b, resulting in initiation of the cytosolic process of complement
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
Substrates: -
Products: -
Products: -
?
complement component C3 + H2O
complement component C3a + complement component C3b
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
Substrates: -
Products: -
Products: -
?
complement component C5 + H2O
complement component C5a + complement component C5b
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme has a very short half-life. Dissociation of the two noncovalently bound subunits proceeds with a half-life of 1-3 min at 37°C under physiological conditions, and this rate increases greatly if regulatory proteins are present. Numerous decay-accelerating proteins are present in plasma and on host cells that bind to the noncatalytic subunit C3b and increase the rate at which the catalytic subunit Bb is released into the medium. Bb loses its enzymatic activity and its ability to bind to C3b upon release. Although C3b is able to rebind Bb and reform the enzyme, the interaction with most decay-accelerating factors also leads to permanent proteolytic interaction of the cell-bound subunit C3b by a fluid-phase protease Factor I. These regulatory events limit cleavage of C3, reduce release of the anaphylatoxin C3a and control the formation of more efficient C5 convertase enzymes
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in the alternative pathway of human complement
Products: -
Products: -
?
additional information
?
-
-
Substrates: the activation peptide, C5a, possesses potent spasmogenic and chemotactic activity
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
-
the C5 convertase is a serine protease that consists of two subunits: a catalytic subunit which is bound in a Mg2+-dependent complex to a noncatalytic subunit
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ab (2B7)
inhibits the deposition of C3b on Escherichia coli in hemolymph plasma, whereas it exhibits no inhibitory effect on the deposition of C3b on Staphylococcus aureus
-
Aurin tricarboxylic acid
blocks the alternative pathway at a downstream step from C3b attachment. It prevents formation of C3 convertase at the stage where Factor B, attached to the membrane-bound properdin-C3b-Factor B (PC3bB) complex, is cleaved by the protease action of Factor D to form the active C3 convertase enzyme PC3bBb. Activity is restored by the addition of excess Factor D to the serum. But membrane attack complex formation is still blocked by ATA at the stage of C9 addition to C5b678. It has no effect on the classical pathway activation. Binding of aurin tricarboxylic acid to the QPDTIDHDLLLLQLS site blocks the ability of aurin tricarboxylic acid to bind to Factor D protein
C3b-specific antibody fragment S77
-
inhibits the alternative pathway C5 convertase in human serum
-
complement factor H-related protein 1
-
0.005-0.16 mg/ml inhibits C5 convertase activity
-
complement receptor 1
CR1, mediates decay acceleration of the C3bBb complex
-
complement receptor of immunoglobulin family
-
the inhibitor blocks both C3 and C5 conversion
-
CRIg
phagocytic receptor, binds to the beta-chain of complement components C3b and C3c and inhibits the AP C3 and C5 convertases, structure-activity relationship of CRIg mutants indicated
-
decay accelerating factor
DAF, mediates decay acceleration of the C3bBb complex
-
decay-accelerating factor
DAF, CD55, major site of interaction with the larger cleavage subunit complement component factor B (Bb), interaction pathway dissected, second short consensus repeat (SCR) domain of DAF (SCR2) interacts only with fragment Bb, whereas SCR4 interacts with complement component C3b, SCR3 does not directly interact with either subunit
-
Efb-C
-
C-terminal region of extracellular fibrinogen binding protein. The inhibitor specifically blocks C5 conversion, while leaving C3 conversion unaffected
-
extracellular complement binding protein
-
the inhibitor specifically blocks C5 conversion, while leaving C3 conversion unaffected
-
factor H related-protein 5
-
inhibits C5 conversion in a concentration-dependent manner
-
hC3Nb3
-
purified recombinant protein expressed in LOBSTR orHEK293F cells. The nanobody hC3Nb3, which is specific for the C-terminal C345c domain of human and mouse complement component C3/C3b/C3c, potently inhibits C3 cleavage by both the alternative pathway and the terminal pathway. Although the nanobody does not affect classical pathway-mediated C3 cleavage, hC3Nb3 inhibits classical pathway-driven hemolysis, suggesting that the C-terminal domain of C3b has an important function in classical pathway C5 convertase activity. The hC3Nb3 nanobody binds C3 with low nanomolar affinity in an SDS-resistant complex, and the nanobody is demonstrated to be a powerful reagent for C3 detection in immunohistochemistry and flow cytometry. hC3Nb3 binding analysis with the C-terminal part of the murine C3 domain (murine C3 C345c domain, residues 1517-1663). hC3Nb3 does not interfere with substrate binding by the C3 convertase, whereas it competes with FB for binding to C3b. hC3Nb3 inhibits AP C3 degradation. hC3Nb3 displays low inhibition potential in the murine system. This may indicate that in serum, the nanobody is less efficient at binding to the murine C3 C345c domain compared with the homologous human domain
-
hemocyanin-depleted plasma
preincubation of hemocyanin-depleted plasma with the anti-factor C Ab (2B7) dose-dependently inhibits the proteolytic conversion of C3 to C3b in the presence of LPS
-
hydroxylamine
inactivates the thioester bond on C3, dramatically decreases the deposition of C3b on microbes
OmCI
-
the inhibitor blocks C5 cleavage by interfering with convertase recognition far from C5a
-
Ornithodoros moubata complement inhibitory protein
-
the inhibitor specifically interfers with C5 conversion but not C3 conversion
-
Pra1
-
i. e. Candida albicans complement regulator acquiring surface protein 2 or pH-regulated Ag 1. In the direct surrounding of the pathogen, inhibitor binds to fluid-phase C3, blocks cleavage of C3 to C3a and C3b and inhibits complement activation via the alternative and classical pathways. In addition, the release of the anaphylatoxins C3a and C5a, as well as C3b/iC3b surface deposition, is reduced. By reducing C3b/iC3b levels at the yeast surface, Pra1 decreases complement-mediated adhesion, as well as uptake of Candida albicans by human macrophages
-
SSL7
-
the inhibitor blocks C5 cleavage by interfering with convertase recognition far from C5a
-
thioredoxin 1
Trx-1, causes significant inhibition of alternative convertases, mechanism, overview. Trx-1 is capable of inhibiting all classical and alternative convertases but its effect is more pronounced in inhibition of alternative ones
eculizumab
-
the inhibitor specifically interfers with C5 conversion but not C3 conversion
-
staphylococcal complement inhibitor
-
from Staphylococcus aureus, binds and blocks active convertases in solution and induced dimerization of C3bBb
-
TT30
-
therapeutic fusion protein linking the human complement receptor type 2 C3 fragment-binding domain with the CAP inhibitory domain of human factor H. TT30 efficiently blocks ex vivo CAP-dependent accumulation of C3-fragment on activated surfaces, membrane attack complex formation and hemolysis of red blood cells, without interference of C3 activation or membrane attack complex formation
-
TT30
-
complement alternative pathway-selective inhibitor, fusion protein linking the first four short consensus repeats of human complement receptor type 2 with the first five short consensus repeats of human factor H
-
additional information
-
eculizumab does not block the activity of the APC C3 convertase
-
additional information
-
the anti-factor B autoantibody binds to factor B and to the alternative pathway C3 convertase and alters the kinetics of complement activation and regulation, the anti-factor B autoantibody does not influence the assembly of the C3 convertase
-
additional information
addition of guinea pig serum in 40 mM EDTA initiates lysis of existing convertase complexes and excludes the possibility of de novo convertase formation
-
additional information
regulatory proteins inactivate C3/C5 convertases on host surfaces to avoid collateral tissue damage
-
additional information
-
CVF, Bb and CVF exhibit complete resistance to the regulatory proteins factors H and I
-
additional information
the anticoagulogen Ab (14E7) has no effect on the conversion of C3. Abs against coagulation factor G (monoclonal) and the proclotting enzyme (polyclonal) do not inhibit the deposition of C3b on Escherichia coli
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
C3b
-
C3b product of the CVFB proconvertase reaction is functional in CP C5 convertase activity
-
factor C
acts as an LPS-responsive C3 convertase on the surface of invading Gram-negative bacteria in the initial phase of horseshoe crab complement activation. The proteolytic activity of factor C on the surface of Escherichia coli is essential for the deposition of C3b
-
formyl-methionyl-leucylphenylalanine
-
treatment of whole blood leads to stimulation of neutrophils resulting in activation of the alternative complement pathway and release of C5 fragments, which further amplify proinflammatory responses
human complement factor H-related protein 4
CFHR 4, two isozymes A and B of 86 and 45 kDa from plasma, domain structure, overview. The protein belongs to the factor H family of plasma glycoproteins that are composed of short consensus repeat (SCR) domains. It activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein. CFHR4 binds C3b via its C-terminus, and it lacks SCRs homologous to the complement inhibitory domains of factor H and has no significant complement regulatory activities. In contrast to the complement inhibitor factor H, CFHR4 acts as an enhancer of opsonization by promoting complement activation
-
LPS
proteolytic conversion of C3 to C3b in hemocyanin-depleted plasma is strongly induced by LPS
-
phorbol myristate acetate
-
treatment of whole blood leads to stimulation of neutrophils resulting in activation of the alternative complement pathway and release of C5 fragments, which further amplify proinflammatory responses
tumor necrosis factor-alpha
-
treatment of whole blood leads to stimulation of neutrophils resulting in activation of the alternative complement pathway and release of C5 fragments, which further amplify proinflammatory responses
-
zymosan
it is capable of activating the classical pathway as well as the alternative pathway, when the classical pathway is blocked, mechanism, overview
-
factor B
generation of the AP C3-convertase initiates by the binding of factor B to C3b to form the proconvertase, C3bB. Factor B undergoes a dramatic conformational change upon binding to C3b, it binds near the C345C domain in C3b. Factor B-D279G mutant promotes high-affinity C3b-binding and is correctly cleaved by factor D in the C3bB proenzyme to generate a very stable, functionally-active, AP C3-convertase C3bBb
-
factor B
the classical C5 convertase requires factor D and factor B for activation and complex assembly
-
factor D
the proconvertase C3bB is cleaved by factor D at a single site in factor B, producing Ba and Bb fragments. Ba dissociates from the complex, while Bb remains bound to C3b, forming the active AP C3-convertase C3bBb
-
factor D
the classical C5 convertase requires factor D and factor B for activation and complex assembly
-
mannan-binding lectin
-
binding to O antigen-specific oligosaccharides derived from Salmonella sp. corresponding to serogroup C, and efficient support of component C3 deposition in the absence of C2, C4, or the associated serine protease 2
-
mannan-binding lectin
mannan-binding lectin (MBL) promotes activation of complement component C3 through the combined action of MBL-associated serine proteases MASP-1 and MASP-2 without appreciable involvement of the alternative pathway, experimental conditions described
-
mannan-binding lectin
mannan-binding lectin (MBL) promotes activation of complement component C3 through the combined action of MBL-associated serine proteases MASP-1 and MASP-2 without appreciable involvement of the alternative pathway
-
properdin
-
surface plasmon resonance assays, properdin promotes the association of C3b with factor B and provides a focal point for the assembly of enzyme on a surface. Properdin can use its unoccupied C3b-binding sites as receptors and form a lattice of properdin-C3b, -C3bB and C3bBb complexes leading to in situ assembly of enzyme
-
properdin
facilitates AP complement activation by stabilizing the C3 convertase C3bBb, essential for AP complement activation induced by bacterial lipopolysacharide (LPS) and lipooligosacharide (LOS) and other AP complement activators
-
properdin
positive regulator of the alternative pathway, no direct interaction with the decay-accelerating factor DAF determined
-
properdin
properdin (Factor P) binding to the erythrocyte membranes is necessary for C3b to attach and initiate alternative pathway activation
-
properdin
-
a highly positively charged plasma glycoprotein, encoded by the X chromosome. Serum properdin is essential for LPS and zymosan-induced C5b-9 generation and C5b-9-mediated lysis of rabbit erythrocytes. It plays an essential role in C5 cleavage by AP convertases. Properdin inhibitor is Salp20. In contrast to most complement proteins that are produced by the liver, properdin is mainly synthesized by leukocytes. Properdin stabilizes AP convertases in two ways. First, it holds the two components of the convertase complex, C3b and Bb, together via TSR5 and TSR6 of the vertex structure that bridge C3b to Bb. Second, binding of properdin limits the action of negative convertase regulators. Properdin competes with FI for the binding to the convertase and makes the convertase less vulnerable to decay acceleration by complement regulators
-
properdin
facilitates AP complement activation by stabilizing the C3 convertase C3bBb, essential for AP complement activation induced by bacterial lipopolysacharide (LPS) and lipooligosacharide (LOS) and other AP complement activators
-
additional information
-
complement activation via the lectin pathway on zymosan particles is at least 4times more efficient than via the classical pathway on sheep erythrocytes coated with antibody. Every C4b deposited via the lectin pathway is capable of forming a convertase in contrast to only one of four C4b molecules deposited via the classical pathway. Rate of formation of lectin pathway C3/C5 convertases depends on the activation of C4 and C2 by MASP-2
-
additional information
-
high surface density of complement component C3b is critical for the enzyme activity
-
additional information
proteolytic conversion of C3 to C3b in hemocyanin-depleted plasma is not induced by zymosan, peptidoglycan, or laminarin
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000075
complement component C5
-
high-affinity C5 convertase (EMan,C3bC4b,C2a)
-
0.0000086
complement component C5
-
high-affinity C5 convertase (ZymM1,C3bC4b,C2a)
-
0.00124
complement component C5
-
37°C, enzyme ZymC3b,Bb, surface-bound C5 convertase formed on zymosan particles
-
0.00273
complement component C5
-
surface-bound C3/C5 convertase (ZymM1,C4b,C2a)
-
0.0688
complement component C5
-
surface-bound C3/C5 convertase (EMan,M1,C4b,C2a)
-
2.75
t-butyloxycarbonyl-Gly-L-Leu-L-Ala-L-Arg-thiobenzyl ester
subunit Bb, mutant with Cys-residues at positions 428, 435
5.63
t-butyloxycarbonyl-Gly-L-Leu-L-Ala-L-Arg-thiobenzyl ester
subunit Bb, wild-type
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0038
complement component C5
-
37°C, enzyme ZymC3b,Bb, surface-bound C5 convertase formed on zymosan particles
-
0.0082
complement component C5
-
surface-bound C3/C5 convertase (EMan,M1,C4b,C2a)
-
0.011
complement component C5
-
surface-bound C3/C5 convertase (ZymM1,C4b,C2a)
-
0.013
complement component C5
-
high-affinity C5 convertase (ZymM1,C3bC4b,C2a)
-
0.28
t-butyloxycarbonyl-Gly-L-Leu-L-Ala-L-Arg-thiobenzyl ester
subunit Bb, mutant with Cys-residues at positions 428, 435
0.65
t-butyloxycarbonyl-Gly-L-Leu-L-Ala-L-Arg-thiobenzyl ester
subunit Bb, wild-type
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00002
soluble complement receptor type 1
Homo sapiens
-
at 37°C, pH not specified in the publication
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
ability of human properdin to restore LPS-dependent AP complement activity in properdin-deficient mouse serum shown to be correlated with the human properdin-binding affinity of the LPS
additional information
-
ability of human properdin to restore LPS-dependent AP complement activity in properdin-deficient mouse serum shown to be correlated with the human properdin-binding affinity of the LPS
additional information
deposition of the solid-phase activation product complement component C3b on a mannan-coated surface at a high concentration of 17% of human serum determined, function of the proteases MASP-1 and MASP-2 in the generation of complement component C3 convertase at high but not at low serum concentrations
additional information
hemolysis assay to assess inhibition by DAF mutants described, equilibrium analysis of recombinant soluble DAF mutants binding to complement component C3b shown, kinetic constants for binding of DAF mutants to the complement component C3b and fragment Bb and ability to decay AP convertase determined, interaction of DAF with properdin and decay of properdin-stabilized convertase indicated, binding kinetics of fragment Bb to recombinant soluble DAF mutants DAF1234, DAF23 and DAF34 determined, decay of AP C3 convertase by DAF and DAF mutants monitored
additional information
convertase formation and activity shown, Western blot, ELISA and fluorescence resonance energy transfer (FRET) used to study formation of the fluid-phase AP convertases C3(H2O)Bb and C3bBb, regulation by factor H and factor I determined, higher affinity for complement component C3(H2O) than for complement component C3b determined, convertase activity of C3bBb higher than of C3(H2O)Bb, C3(H2O)Bb convertase more resistant to inactivation by factor H and factor I than the C3bBb convertase, 25% of initial activity of complement component C3(H2O)Bb retained at conditions that totally inactivate C3bBb
additional information
central role of the amplification loop in complement activation discussed, development of a model placing the amplification loop at the center of the complement system as a means to expand complement component C3/C5 activation and irrespective of the origin of the triggering complement component C3b molecules
additional information
plasma levels of complement components determined in patients with severe trauma
additional information
LPS- and LOS-induced AP complement activation abolished in properdin-deficient mouse serum, zymosan- and cobra venom factor-induced AP complement activation observed, classical pathway-triggered AP complement amplification only partially or minimally affected in properdin-deficient mice, ability of human properdin to restore LPS-dependent AP complement activity in properdin-deficient mouse serum shown to be correlated with the human properdin-binding affinity of the LPS
additional information
-
LPS- and LOS-induced AP complement activation abolished in properdin-deficient mouse serum, zymosan- and cobra venom factor-induced AP complement activation observed, classical pathway-triggered AP complement amplification only partially or minimally affected in properdin-deficient mice, ability of human properdin to restore LPS-dependent AP complement activity in properdin-deficient mouse serum shown to be correlated with the human properdin-binding affinity of the LPS
additional information
complement component C3 cleavage through the mannan-binding lectin (MBL) pathway in mouse sera determined, experimental conditions described
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
36593, 36594, 36595, 36596, 36597, 36598, 36599, 36600, 36601, 36602, 36603, 649689, 649815, 652225, 652672, 668899
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
existence of a mannan-binding lectin-dependent C2 bypass mechanism for alternative pathway-mediated C3 activation
brenda
human serum from B/B genotype donors deficient in mannan-binding lectin (MBL)
brenda
C3 knock-out mice used as an assay control, serum from MBL double-KO mice (MBLA-/-, MBLC-/-) used to evaluate the mannan-binding lectin (MBL) pathway
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
-
enzyme inhibition with eculizumab blunts terminal complementxa0activation in patients with immunexa0complex-mediated primary membranoproliferative glomerulonephritis or C3 glomerulonephritis and nephrotic syndrome
malfunction
-
C3 glomerulopathies (C3G) are ultra-rare complement-mediated diseases that lead to end-stage renal disease (ESRD) within 10 years of diagnosis in about 50% of patients. Overactivation of the alternative pathway (AP) of complement in the fluid phase and on the surface of the glomerular endothelial glycomatrix is the underlying cause of C3G. C3G pathogenesis is primarily driven by dysregulation of complement in the circulation and/or glomerular microenvironment. Complement is an integral part of the innate immune system, responsible for pathogen clearance and recruitment of immune cells to the site of complement activation. In C3G, C3 convertase regulation is impaired, resulting in complement deposits in the renal glomeruli. Mechanism of C3Nef-mediated C3G pathogenesis, overview
metabolism
-
when factor B first associates with C3b, it bears two intact Arg234 salt bridges. The complex rapidly dissociates unless the Arg234-Glu446 salt bridge is released whereupon conformational changes occur that activate the metal ion-dependent adhesion site and partially stabilize the complex. The remaining salt bridge is then released, exposing the scissile bond and permitting factor D cleavage of proenzyme factor B
metabolism
complement activation results in the assembly of unstable protease complexes, denominated C3/C5 convertases, leading to inflammation and lysis. Regulatory proteins inactivate C3/C5 convertases on host surfaces to avoid collateral tissue damage. On pathogen surfaces, the glycoprotein properdin stabilizes C3/C5 convertases to efficiently fight infection. The N- and C-terminal ends of adjacent monomers in properdin oligomers conform a curly vertex that holds together the AP convertase, interacting with both the C345C and vWA domains of C3b and Bb, respectively. Properdin also promotes a large displacement of the TED (thioestercontaining domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domains of C3b, which likely impairs C3-convertase inactivation by regulatory proteins
metabolism
all pathways converge at the level of the C3 molecule, where downstream events can be amplified by a mechanism of positive feedback supported by complement convertases: the classical/lectin pathway C3 convertase (C4b2a) or the alternative pathway C3 convertase (C3bBb). These convertases further cleave C3 to C3b and C3a, of which C3b binds to nearby surfaces, providing a convertase assembly platform, or to pre-assembled C3 convertases, switching them to C5 convertases (C4b2aC3b or C3bBbC3b, respectively). The C5 convertase cleaves C5 molecules to C5a and C5b and the latter initiates formation of the membrane attack complex (MAC, C5b678polyC9) and its insertion into a target membrane. Enzyme regulation, overview
metabolism
-
complement is an integral part of the innate immune system, responsible for pathogen clearance and recruitment of immune cells to the site of complement activation. Of the three complement-initiating pathways (classical, lectin, alternative), the alternative pathway (AP) is the main contributor to C3G pathogenesis. The AP is continuously activated at a low rate in a process known as tick-over, resulting in cleavage of complement component 3 (C3) into an anaphylatoxin C3a and an opsonin C3b, which deposits on pathogen and self surfaces to drive formation of C3 convertase of the AP, C3bBb. This process is tightly controlled by regulators of complement activation (RCA) which control complement activity to prevent injury to the host
metabolism
-
alternative complement system regulation by factors and nanobodies, overview
physiological function
the alternative pathway is activated by zymosan in human serum after blocking the classical pathway activation with either a polyclonal antibody to C4d or with C1 inhibitor. Properdin (Factor P) binding to the erythrocyte membranes is necessary for C3b to attach and initiate alternative pathway activation, regulation, overview
physiological function
Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein. Ability of CFHR4-bound C3b to bind factor B and properdin, leading to an active convertase that generates C3a and C3b from C3. The CFHR4-C3bBb convertase is less sensitive to the factor H-mediated decay compared with the C3bBb convertas. In contrast to the complement inhibitor factor H, CFHR4 acts as an enhancer of opsonization by promoting complement activation
physiological function
-
both the in situ conversion of complement component C5 by the enzyme and immediate association of C5b with C6 and C7 are needed to guide proper insertion of bactericidal MAC pores
physiological function
-
the complement system is an important part of innate immunity. Complement activation leads to formation of convertase enzymes, switch of their specificity from C3 to C5 cleavage, and generation of lytic membrane attack complexes (C5b-9) on surfaces of pathogens. The C5 convertase initiates the complement terminal pathway by cleaving C5 into C5a and C5b. C5a is released as a very potent anaphylatoxin. C5b interacts with C6, C7, C8, and multiple copies of C9 to form the C5b-9 complex, also known as the membrane attack complex. This complex forms a porelike structure that perforates the membrane and induces cell lysis or metabolic cell stress of the potentially harmful targets. Most C5 cleavage occurs via the complement alternative pathway (AP). The regulator properdin promotes generation and stabilization of AP convertases. Essential role of properdin in C5 convertase activity and C5b-9 formation in the complement alternative pathway, overview. Properdin is essential for the convertase specificity switch toward C5, and this function is independent of properdin's role in new convertase formation
physiological function
-
the complement system is an intricate cascade of the innate immune system and plays a key role in microbial defense, inflammation, organ development, and tissue regeneration. The C3 convertase is responsible for the formation of C3a and C3b from the C3 zymogen. The nanobody hC3Nb3, which is specific for the C-terminal C345c domain of human and mouse complement component C3/C3b/C3c and potently inhibits C3 cleavage by the alternative pathway. The C3b product of the C3 proconvertase reaction is functional in classical pathway C5 convertase activity
physiological function
-
cobra venom factor (CVF) is the complement-activating protein in cobra venom. CVF is a structural and functional analogue of complement component C3. CVF, like C3b, forms a convertase with factor B. This bimolecular complex CVF, Bb is an enzyme that cleaves C3 and C5. However, CVF, Bb exhibits significantly different functional properties from C3b, Bb. Whereas both, CVF, Bb and C3b, Bb exhibit spontaneous decay-dissociation into the respective subunits, thereby eliminating the enzymatic activity, the CVF, Bb convertase is physico-chemically far more stable, decaying with a half-life that is more than two orders of magnitude slower than that of C3b, Bb. In addition, CVF, Bb is completely resistant to inactivation by factors H and I. These two properties of CVF, Bb allow continuous activation of C3 and C5, and complement depletion in serum
additional information
stabilization of the complement alternative pathway C3 convertase by properdin, structural basis, overview. Complex assembly between properdin and C3 convertase by incubation of C3b, Factor B, and Factor D in the presence of properdin. The Factor B-D279G mutant increases the stability of C3 convertase. Properdin cross-Links C3b and the Bb fragment, stabilizing the C3bBb convertase, structure overview
additional information
the classical C5 convertase requires factor D and factor B for activation and complex assembly
additional information
-
development of a hemolytic assay in which AP convertases are generated on rabbit erythrocytes by using properdin-depleted serum in the presence of C5 inhibitor, followed by washing and addition of purified C5-C9 components to allow C5b-9 formation. In the assay, addition of purified properdin to properdin-depleted serum during convertase formation is required to restore C5 cleavage and C5b-9-mediated hemolysis. Importantly, C5 convertase activity is also fully restored when properdin is added together with C5b-9 components, thus after convertase formation. With C3-depleted serum, not capable of forming new convertases but containing properdin, in step 2 of the assay, again full C5b-9 formation is observed and blocked by addition of properdin inhibitor Salp20
Show AA Sequence and Transmembrane Helices (343 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
fragment Bb, MW 63000 Da, is the catalytic subunit of the enzyme
additional information
-
the C5 convertase is a serine protease that consists of two subunits: a catalytic subunit which is bound in a Mg2+-dependent complex to a noncatalytic subunit. The binding site for c5 resides in the noncatalytic subunit of the enzyme, the affinity for the substrate is solely determined by the noncatalytic subunit and the catalytic efficiency of the enzyme appears to to be influenced by the nature of this subunit
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
cobra venom factor (CVF) is a glycoprotein with unusual glycosylation, but CVF glycosylation is of no functional relevance
proteolytic modification
-
association of factor B with C3b in the presence of Mg2+ results in the formation of a bimolecular zymogen C3b,B, which is activated by the serine proteinase factor D, generating the C3 convertase, C3b,Bb
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
C3 convertase formed by C3b and the protease fragment Bb in complex with staphylococcal complement inhibitor, hanging drop vapor diffusion method, using 75 mM sodium/potassium tartrate, 8.0% (w/v) PEG 3350, 50 mM Bis-Tris propane, pH 6.5
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crystal structures of the pro-convertase C3bB at 4 A resolution and its complex with factor D at 3.5 A resolution. Factor B binding to C3b forms an open activation state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor Ds self-inhibitory loop. This concerted proteolytic mechanism, which is cofactordependent and substrate-induced, restricts complement amplification to C3b-tagged target cells
engineered subunit Bb with Cys-resiudes at positions 435 and 428, in complex with inhibitors 6-amidino-2-naphthyl-4-guanidinobenzoate or diisopropyl phosphate
in complex with factor H, hanging drop vapor diffusion method, using 7.0% (w/v) PEG 3350, 70 mM ammonium acetate, pH 7.1, at 18°C
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structural analysis of complement component C3b in complex with the macrophage-expressed complement receptor CRIg, domain architecture of complement component C3 and the C3b/C3c-CRIg complexes shown, structural similarities between complement components C3b and C3c indicated, comparison between complement components C3b and C3 reveals that complement component C3 stimulation is accompanied by major strucural rearrangements
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
923DELTADG
-
mutation in complement factor 3 gene identified in patients with dense deposit disease. Mutant C3923DELTADG, which lacks 2 amino acids, cannot be cleaved to C3b by the alternative pathway C3-convertase and is therefore the predominant circulating C3 protein in the patients. Upon activation to C3b by proteases, or to C3(H2O) by spontaneous thioester hydrolysis, mutant C3 generates an active C3-convertase that is regulated normally by decay accelerating factor but is resistant to decay by factor H. Activated C3b923DELTADG and C3(H2O)923DELTADG are resistant to proteolysis by factor I in the presence of factor H, but are efficiently inactivated in the presence of membrane cofactor protein, causing a fluid phase-restricted alternative pathway dysregulation in the patients that continuously activates and consumes C3 produced by the normal C3 allele
D254G
-
mutation in the Bb component decreases sensitivity to DAF to 9% of the wild-type value, sensitivity to CR1 to 4% of the wild-type value and sensitivity to Factor H to 48% of the wild-type value
D382A
-
mutation in the Bb component decreases sensitivity to DAF to 36% of the wild-type value, sensitivity to CR1 to 41% of the wild-type value
D382N
-
mutation in the Bb component decreases sensitivity to DAF to 54% of the wild-type value
D445A
-
mutation in the Bb component decreases sensitivity to CR1 to 71% of the wild-type value
D715A
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factor B mutation, severly reduces hemolytic activity, in complex with C3b no cleavage of C3
D715E
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factor B mutation, severly reduces hemolytic activity, in complex with C3b no cleavage of C3
D715N
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factor B mutation, severly reduces hemolytic activity, in complex with C3b no cleavage of C3
E207A
-
mutation in proenzyme factor B. Mutation disrupts salt bridge R234-E207, with little effects on the cleavage of proenzyme factor B
E301A
-
mutation in the Bb component decreases sensitivity to DAF to 75% of the wild-type value
E316A
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mutation in the Bb component decreases sensitivity to DAF to 71% of the wild-type value
E379A
-
mutation in the Bb component decreases sensitivity to DAF to 52% of the wild-type value, sensitivity to CR1 to 50% of the wild-type value
E434A
-
mutation in the Bb component decreases sensitivity to CR1 to 65% of the wild-type value
E446V
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mutation in proenzyme factor B. Mutation disrupts salt bridge R234-E446 which partly stabilizes the complex C3bB(Mg2+) thereby inhibiting activation of the proenzyme
K265A/K266A
-
Mutation in the Bb component decreases sensitivity to DAF to 18% of the wild-type value, sensitivity to CR1 to 18% of the wild-type value and sensitivity to Factor H to 19% of the wild-type value
K294A
-
mutation in the Bb component decreases sensitivity to CR1 to 44% of the wild-type value
M341A
-
mutation in the Bb component decreases sensitivity to Factor H to 75% of the wild-type value
N260D
-
mutation in the Bb component decreases sensitivity to DAF to 32% of the wild-type value, sensitivity to CR1 to 31% of the wild-type value and sensitivity to Factor H to 24% of the wild-type value
Q335A
-
mutation in the Bb component decreases sensitivity to DAF to 20% of the wild-type value
S339A
-
mutation in the Bb component decreases sensitivity to DAF to 32% of the wild-type value, sensitivity to CR1 to 50% of the wild-type value
W343A
-
mutation in the Bb component decreases sensitivity to DAF to 55% of the wild-type value, sensitivity to CR1 to 56% of the wild-type value
Y338A
-
mutation in the Bb component decreases sensitivity to DAF to 9% of the wild-type value, sensitivity to CR1 to 4% of the wild-type value and sensitivity to Factor H to 48% of the wild-type value
Y338F
-
mutation in the Bb component decreases sensitivity to DAF to 18% of the wild-type value, sensitivity to CR1 to 20% of the wild-type value and sensitivity to Factor H to 61% of the wild-type value
Y338S
-
mutation in the Bb component decreases sensitivity to DAF to 5% of the wild-type value, sensitivity to CR1 to 24% of the wild-type value
additional information
additional information
-
replacement of C-terminal sequences of enzyme compoment C3 by the corresponding sequences of cobra venom factor from Naja kaouthia. Major role of NTR/C345C motiv in regulation of enzyme half-life
additional information
-
substitution of enzyme component C3 domains by corresponding domains of cobra venom factor. Structural domains of cobra venom factor gamma- or beta-chains confer stability to C3 convertase complex. Replacement of terminal C-275 amino acids by those of cobra venom factor beta-chain results in a catalytic activity of C3 convertase similar to wild-type, but with a half-life of 5-6 h compared to 1-2 min for wild-type
additional information
introduction of Cys-residues to form a disulfide bond at positions 428 and 435 of von Willebrandt factor type A domain of subunit Bb. Adaption of an active conformation by the domain, which is not sufficient to activate the enzyme catalytic apparatus
additional information
-
an in vitro model of AP activation and regulation on a glycomatrix surface in constructed using an extracellular matrix substitute (MaxGel) as a base upon which AP C3 convertase is reconstituted, method evaluation using properdin and Factor H (FH) and assessment of the effects of genetic and acquired drivers of C3G on C3 convertase. C3 convertase readily forms on MaxGel and this formation is positively regulated by properdin and negatively regulated by FH. FH inhibits C3 convertase formation on the extracellular matrix surface in dose-dependent manner. Factor B (FB) and FH mutants impair complement regulation when compared to wild-type counterparts. Effects of antibodies against AP C3 convertase called C3 nephritic factors (C3Nefs) on convertase stability over time, overview. IgG derived from C3Nef-positive C3G patients stabilize C3 convertase, some promote formation. Pathogenic variation in SCR 1-3 of CFH leads to decrease inhibitory function of FH on ECM surface
additional information
-
enzyme component C3 deletion mutant. Acute lung inflammatory injury is greatly attenuated in lungs of mutant animals, and C5a levels in broncheolar lavage fluids of mutants greatly reduced in presence of antithrombin III or hirudin, compared to wild-type. Plasma from mutant animals contains threefold higher levels of thrombin activity and higher levels of prothrombin mRNA, prothrombin and thrombin protein in liver of mutants
additional information
-
creation of recombinant hybrid proteins of CVF and human C3 (HC3-1550-4, HC3-1496-9, and HC3-1496-25), based on structural differences between CVF and human C3b in the C-terminal C345C domain. Three human C3/CVF hybrid proteins are synthesized which differ in only one, two, or five amino acid residues from earlier described hybrid proteins. The overall protein sequence identity of all hybrid proteins to human pre-pro-C3 is between 94.3% and 95.6%, with protein sequence similarity ranging from 96.2% to 96.9%. In all three cases, the hybrid proteins containing CVF residues form more stable convertases, and exhibit stronger complement-depletion activity than hybrid proteins with human C3 residues. Three bonds between CVF residues and factor Bb residues are identified by crystallographic modeling that contribute to the greater stability of the convertases
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
intermolecular bonds between human factor B and Ccobra venom factor important for C3 convertase stability
-
marked stabilization of enzyme by naturally occuring IgG directed against the enzyme. Antibody prevents convertase decay in the presence of factor H. In addition, the antibody stabilizes enzyme precursors and promotes enzyme assembly
-
properdin stabilizes enzyme-IgG complexes before any other complement protein has bound to them. The alternative pathway of convertase generation may depend on whether properdin is bound to its precursor, a C3b or a C3b2-IgG complex
-
the enzyme has a very short half-life. Dissociation of the two noncovalently bound subunits proceeds with a half-life of 1-3 min at 37°C under physiological conditions, and this rate increases greatly if regulatory proteins are present. Numerous decay-accelerating proteins are present in plasma and on host cells that bind to the noncatalytic subunit C3b and increase the rate at which the catalytic subunit Bb is released into the medium. Bb loses its enzymatic activity and its ability to bind to C3b upon release. Although C3b is able to rebind Bb and reform the enzyme, the interaction with most decay-accelerating factors also leads to permanent proteolytic interaction of the cell-bound subunit C3b by a fluid-phase protease Factor I. These regulatory events limit cleavage of C3, reduce release of the anaphylatoxin C3a and control the formation of more efficient C5 convertase enzymes
-
the enzyme is subject to irreversible dissociation by three proteins: DAF, CR1 and factor H
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
C3bB(Ni2+) complex or C3bBb(factor B-D279G mutant) purified by gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Streptococcus pneumoniae induces increased gene expression of factor B of the alternative complement pathway and C3 in mouse middle ear epithelium. Activation of factor B and C3 in the middle ear lavage fluids is significantly greater than in simultaneously obtained serum samples
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
patient with membranoproliferative glomerulonephritis, preparation of naturally occuring antibodies to enzyme exhibits nephritic factor activity 60fold stronger than total IgG. Antibodies promote enzyme generation, when added to the convertase precursor or during convertase assembly
medicine
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intervention in complement-mediated pathologies by modulation of enzyme half-life through replacement of enzyme compoment C3 by the corresponding sequences of cobra venom factor from Naja kaouthia
medicine
-
therapeutic reduction of complement activity in vivo by use of engineered enzyme component C3 resulting in greatly improved half-life of C3 convertase
medicine
studies on role of properdin in AP complement initiation for understanding the selective predisposition of properdin-deficient patients to meningococcal infection
medicine
studies on role of properdin in AP complement initiation for understanding the selective predisposition of properdin-deficient patients to meningococcal infection
medicine
clinical significance of early complement stimulation in trauma patients analyzed, complement stimulation, particularly alternative pathway related to clinical outcomes in patients with severe trauma
medicine
-
activation of complement via the lectin pathway may be a more prominent contributor to the pathology of inflammatory reactions as compared to activation of complement via the classical pathway
medicine
-
Streptococcus pneumoniae induces increased gene expression of factor B of the alternative complement pathway and C3 in mouse middle ear epithelium. Activation of factor B and C3 in the middle ear lavage fluids is significantly greater than in simultaneously obtained serum samples. Complement C3 activation and opsonophagocytosis of Streptococcus pneumoniae are greatly attenuated in factor B- and factor B/C2-deficient mice. Local complement activation is an important host innate immune response and activation of the alternative complement pathway represents one of the innate immune defense mechanisms against pneumococcal infection during the early stage of acute otitis media
medicine
-
mutation 923DELTADG in complement factor 3 gene is identified in patients with dense deposit disease. Mutant C3923DELTADG, which lacks 2 amino acids, cannot be cleaved to C3b by the alternative pathway C3-convertase and is therefore the predominant circulating C3 protein in the patients. Upon activation to C3b by proteases, or to C3(H2O) by spontaneous thioester hydrolysis, mutant C3 generates an active C3-convertase that is regulated normally by decay accelerating factor but is resistant to decay by factor H. Activated C3b923DELTADG and C3(H2O)923DELTADG are resistant to proteolysis by factor I in the presence of factor H, but are efficiently inactivated in the presence of membrane cofactor protein, causing a fluid phase-restricted alternative pathway dysregulation in the patients that continuously activates and consumes C3 produced by the normal C3 allele
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pangburn, M.K.; Muller-Eberhard, H.J.
The C3 convertase of the alternative pathway of human complement. Enzymic properties of the bimolecular proteinase
Biochem. J.
235
723-730
1986
Homo sapiens
brenda
DiScipio, R.G.; Smith, C.A.; Muller-Eberhard, H.J.; Hugli, T.E.
The activation of human complement component C5 by a fluid phase C5 convertase
J. Biol. Chem.
258
10629-10636
1983
Homo sapiens
brenda
Gutierrez, J.C.; Gtze, O.; Caporale, L.H.
An improved fluorogenic substrate for the alternative complement pathway C3/5 converting enzyme CVFBb
Biochim. Biophys. Acta
744
276-280
1983
Homo sapiens
brenda
Vogel, C.W.; Muller-Eberhard, H.J.
The cobra venom factor-dependent C3 convertase of human complement. A kinetic and thermodynamic analysis of a protease acting on its natural high molecular weight substrate
J. Biol. Chem.
257
8292-8299
1982
Homo sapiens
brenda
Schwaeble, W.; Luttig, B.; Sokolowski, T.; Estaller, C.; Weiss, E.H.; Meyer zum Bschenfelde, K.H.; Whaley, K.; Dippold, W.
Human complement factor B: functional properties of a recombinant zymogen of the alternative activation pathway convertase
Immunobiology
188
221-232
1993
Homo sapiens
brenda
Williams, S.C.; Sim, R.B.
Dye-ligand affinity purification of human complement factor B and beta 2 glycoprotein I
J. Immunol. Methods
157
25-30
1993
Homo sapiens
brenda
Hourcade, D.E.; Mitchell, L.M.; Oglesby, T.J.
A conserved element in the serine protease domain of complement factor B
J. Biol. Chem.
273
25996-26000
1998
Homo sapiens
brenda
Sumiyoshi, K.; Andoh, A.; Fujiyama, Y.; Sakumoto, H.; Bamba, T.
Characterization of complement C3, C4, and factor B molecules in human bile
J. Gastroenterol.
32
230-235
1997
Homo sapiens
brenda
Fu, Q.; McPhie, P.; Gowda, D.C.
Methionine modification impairs the C5-cleavage function of cobra venom factor-dependent C3/C5 convertase
Biochem. Mol. Biol. Int.
45
133-144
1998
Homo sapiens
brenda
Berkovich, SA.; O'Keefe, M.C.; Hensley, P.; Caporale, L.
Effect of N-methylation on the modulation by synthetic peptides of the activity of the complement-factor-B-derived serine proteinase CVFBb
Biochem. J.
270
531-537
1990
Homo sapiens
brenda
Jelezarova, E.; Vogt, A.; Lutz, H.U.
Interaction of C3b(2)-IgG complexes with complement proteins properdin, factor B and factor H: implications for amplification
Biochem. J.
349
217-223
2000
Homo sapiens
brenda
Pangburn, M.K.; Rawal, N.
Structure and function of complement C5 convertase enzymes
Biochem. Soc. Trans.
30
1006-1010
2002
Homo sapiens
brenda
Hourcade, D.E.; Mitchell, L.; Kuttner-Kondo, L.A.; Atkinson, J.P.; Medof, M.E.
Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb
J. Biol. Chem.
277
1107-1112
2002
Homo sapiens
brenda
Rawal, N.; Pangburn, M.K.
Functional role of the noncatalytic subunit of complement C5 convertase
J. Immunol.
164
1379-1385
2000
Homo sapiens
brenda
Koelln, J.; Bredehorst, R.; Spillner, E.
Engineering of human complement component C3 for catalytic inhibition of complement
Immunol. Lett.
98
49-56
2005
Homo sapiens
brenda
Hourcade, D.E.
The role of properdin in the assembly of the alternative pathway C3 convertases of complement
J. Biol. Chem.
281
2128-2132
2006
Homo sapiens
brenda
Selander, B.; Martensson, U.; Weintraub, A.; Holmstroem, E.; Matsushita, M.; Thiel, S.; Jensenius, J.C.; Truedsson, L.; Sjoeholm, A.G.
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2
J. Clin. Invest.
116
1425-1434
2006
Homo sapiens
brenda
Koelln, J.; Spillner, E.; Andrae, J.; Klensang, K.; Bredehorst, R.
Complement inactivation by recombinant human C3 derivatives
J. Immunol.
173
5540-5545
2004
Homo sapiens
brenda
Ponnuraj, K.; Xu, Y.; Macon, K.; Moore, D.; Volanakis, J.E.; Narayana, S.V.
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase
Mol. Cell
14
17-28
2004
Homo sapiens (P00751)
brenda
Jelezarova, E.; Lutz, H.U.
IgG naturally occurring antibodies stabilize and promote the generation of the alternative complement pathway C3 convertase
Mol. Immunol.
42
1393-1403
2005
Homo sapiens
brenda
Huber-Lang, M.; Sarma, J.V.; Zetoune, F.S.; Rittirsch, D.; Neff, T.A.; McGuire, S.R.; Lambris, J.D.; Warner, R.L.; Flierl, M.A.; Hoesel, L.M.; Gebhard, F.; Younger, J.G.; Drouin, S.M.; Wetsel, R.A.; Ward, P.A.
Generation of C5a in the absence of C3: a new complement activation pathway
Nat. Med.
12
682-687
2006
Mus musculus
brenda
Moller-Kristensen, M.; Thiel, S.; Sjoeholm, A.; Matsushita, M.; Jensenius, J.C.
Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway
Int. Immunol.
19
141-149
2007
Homo sapiens (P00751), Mus musculus (P04186)
brenda
Kimura, Y.; Miwa, T.; Zhou, L.; Song, W.C.
Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement
Blood
111
732-740
2008
Homo sapiens (P00751), Homo sapiens, Mus musculus (P04186), Mus musculus
brenda
Harris, C.L.; Pettigrew, D.M.; Lea, S.M.; Morgan, B.P.
Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay
J. Immunol.
178
352-359
2007
Homo sapiens (P00751)
brenda
Lutz, H.U.; Fumia, S.; Schurtenberger, C.; Alaia, V.
Opinion paper: Stimulation of complement amplification or activation of the alternative pathway of complement?
Mol. Immunol.
44
3862-3865
2007
Homo sapiens (P00751)
brenda
Bexborn, F.; Andersson, P.O.; Chen, H.; Nilsson, B.; Ekdahl, K.N.
The tick-over theory revisited: Formation and regulation of the soluble alternative complement C3 convertase (C3(H(2)O)Bb)
Mol. Immunol.
45
2370-2379
2008
Homo sapiens (P00751)
brenda
Wiesmann, C.; Katschke, K.J.; Yin, J.; Helmy, K.Y.; Steffek, M.; Fairbrother, W.J.; McCallum, S.A.; Embuscado, L.; DeForge, L.; Hass, P.E.; van Lookeren Campagne, M.
Structure of C3b in complex with CRIg gives insights into regulation of complement activation
Nature
444
217-220
2006
Homo sapiens (P00751)
brenda
Ganter, M.T.; Brohi, K.; Cohen, M.J.; Shaffer, L.A.; Walsh, M.C.; Stahl, G.L.; Pittet, J.F.
Role of the alternative pathway in the early complement activation following major trauma
Shock
28
29-34
2007
Homo sapiens (P00751)
brenda
Rawal, N.; Rajagopalan, R.; Salvi, V.P.
Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of complement
J. Biol. Chem.
283
7853-7863
2008
Homo sapiens
brenda
Ariki, S.; Takahara, S.; Shibata, T.; Fukuoka, T.; Ozaki, A.; Endo, Y.; Fujita, T.; Koshiba, T.; Kawabata, S.
Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation
J. Immunol.
181
7994-8001
2008
Tachypleus tridentatus (B6ZH52)
brenda
Torreira, E.; Tortajada, A.; Montes, T.; Rodriguez de Cordoba, S.; Llorca, O.
3D structure of the C3bB complex provides insights into the activation and regulation of the complement alternative pathway convertase
Proc. Natl. Acad. Sci. USA
106
882-887
2009
Homo sapiens (P00751)
brenda
Heinen, S.; Hartmann, A.; Lauer, N.; Wiehl, U.; Dahse, H.M.; Schirmer, S.; Gropp, K.; Enghardt, T.; Wallich, R.; Haelbich, S.; Mihlan, M.; Schloetzer-Schrehardt, U.; Zipfel, P.F.; Skerka, C.
Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation
Blood
114
2439-2447
2009
Homo sapiens
brenda
Roumenina, L.T.; Jablonski, M.; Hue, C.; Blouin, J.; Dimitrov, J.D.; Dragon-Durey, M.A.; Cayla, M.; Fridman, W.H.; Macher, M.A.; Ribes, D.; Moulonguet, L.; Rostaing, L.; Satchell, S.C.; Mathieson, P.W.; Sautes-Fridman, C.; Loirat, C.; Regnier, C.H.; Halbwachs-Mecarelli, L.; Fremeaux-Bacchi, V.
Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome
Blood
114
2837-2845
2009
Rattus norvegicus
brenda
Lindorfer, M.A.; Pawluczkowycz, A.W.; Peek, E.M.; Hickman, K.; Taylor, R.P.; Parker, C.J.
A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement
Blood
115
2283-2291
2010
Homo sapiens
brenda
Katschke, K.J.; Stawicki, S.; Yin, J.; Steffek, M.; Xi, H.; Sturgeon, L.; Hass, P.E.; Loyet, K.M.; Deforge, L.; Wu, Y.; van Lookeren Campagne, M.; Wiesmann, C.
Structural and functional analysis of a C3b-specific antibody that selectively inhibits the alternative pathway of complement
J. Biol. Chem.
284
10473-10479
2009
Homo sapiens
brenda
Torreira, E.; Tortajada, A.; Montes, T.; Rodriguez de Cordoba, S.; Llorca, O.
Coexistence of closed and open conformations of complement factor B in the alternative pathway C3bB(Mg2+) proconvertase
J. Immunol.
183
7347-7351
2009
Homo sapiens
brenda
Strobel, S.; Zimmering, M.; Papp, K.; Prechl, J.; Jozsi, M.
Anti-factor B autoantibody in dense deposit disease
Mol. Immunol.
47
1476-1483
2010
Homo sapiens
brenda
Rooijakkers, S.H.; Wu, J.; Ruyken, M.; van Domselaar, R.; Planken, K.L.; Tzekou, A.; Ricklin, D.; Lambris, J.D.; Janssen, B.J.; van Strijp, J.A.; Gros, P.
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor
Nat. Immunol.
10
721-727
2009
Homo sapiens
brenda
Wu, J.; Wu, Y.Q.; Ricklin, D.; Janssen, B.J.; Lambris, J.D.; Gros, P.
Structure of complement fragment C3b-factor H and implications for host protection by complement regulators
Nat. Immunol.
10
728-733
2009
Homo sapiens
brenda
Laursen, N.S.; Gordon, N.; Hermans, S.; Lorenz, N.; Jackson, N.; Wines, B.; Spillner, E.; Christensen, J.B.; Jensen, M.; Fredslund, F.; Bjerre, M.; Sottrup-Jensen, L.; Fraser, J.D.; Andersen, G.R.
Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus
Proc. Natl. Acad. Sci. USA
107
3681-3686
2010
Homo sapiens
brenda
Camous, L.; Roumenina, L.; Bigot, S.; Brachemi, S.; Fremeaux-Bacchi, V.; Lesavre, P.; Halbwachs-Mecarelli, L.
Complement alternative pathway acts as a positive feedback amplification of neutrophil activation
Blood
117
1340-1349
2011
Homo sapiens
brenda
Fridkis-Hareli, M.; Storek, M.; Mazsaroff, I.; Risitano, A.M.; Lundberg, A.S.; Horvath, C.J.; Holers, V.M.
Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases
Blood
118
4705-4713
2011
Homo sapiens
brenda
Li, Q.; Li, Y.X.; Stahl, G.L.; Thurman, J.M.; He, Y.; Tong, H.H.
Essential role of factor B of the alternative complement pathway in complement activation and opsonophagocytosis during acute pneumococcal otitis media in mice
Infect. Immun.
79
2578-2585
2011
Mus musculus
brenda
Hourcade, D.E.; Mitchell, L.M.
Access to the complement factor B scissile bond is facilitated by association of factor B with C3b protein
J. Biol. Chem.
286
35725-35732
2011
Homo sapiens
brenda
Martinez-Barricarte, R.; Heurich, M.; Valdes-Canedo, F.; Vazquez-Martul, E.; Torreira, E.; Montes, T.; Tortajada, A.; Pinto, S.; Lopez-Trascasa, M.; Morgan, B.P.; Llorca, O.; Harris, C.L.; Rodriguez de Cordoba, S.
Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation
J. Clin. Invest.
120
3702-3712
2010
Homo sapiens
brenda
Luo, S.; Hartmann, A.; Dahse, H.; Skerka, C.; Zipfel, P.
Secreted pH-regulated antigen 1 of Candida albicans blocks activation and conversion of complement C3
J. Immunol.
185
2164-2173
2010
Homo sapiens
brenda
Forneris, F.; Ricklin, D.; Wu, J.; Tzekou, A.; Wallace, R.; Lambris, J.; Gros, P.
Structures of C3b in complex with factors B and D give insight into complement convertase formation
Science
330
1816-1820
2010
Homo sapiens (P01024)
brenda
Hebecker, M.; Jozsi, M.
Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein
J. Biol. Chem.
287
19528-19536
2012
Homo sapiens (P00751), Homo sapiens
brenda
Lee, M.; Guo, J.P.; McGeer, E.G.; McGeer, P.L.
Aurin tricarboxylic acid self-protects by inhibiting aberrant complement activation at the C3 convertase and C9 binding stages
Neurobiol. Aging
34
1451-1461
2013
Homo sapiens (P00751)
brenda
Okroj, M.; Holmquist, E.; King, B.C.; Blom, A.M.
Functional analyses of complement convertases using C3 and C5-depleted sera
PLoS ONE
7
e47245
2012
Homo sapiens (P00751)
brenda
Alcorlo, M.; Tortajada, A.; Rodriguez de Cordoba, S.; Llorca, O.
Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin
Proc. Natl. Acad. Sci. USA
110
13504-13509
2013
Homo sapiens (P00751)
brenda
Ruggenenti, P.; Daina, E.; Gennarini, A.; Carrara, C.; Gamba, S.; Noris, M.; Rubis, N.; Peraro, F.; Gaspari, F.; Pasini, A.; Rigotti, A.; Lerchner, R.M.; Santoro, D.; Pisani, A.; Pasi, A.; Remuzzi, G.; Remuzzi, G.
C5 convertase blockade in membranoproliferative glomerulonephritis a single-arm clinical trial
Am. J. Kidney Dis.
74
224-238
2019
Homo sapiens
brenda
Berends, E.T.; Gorham, R.D.; Ruyken, M.; Soppe, J.A.; Orhan, H.; Aerts, P.C.; de Haas, C.J.; Gros, P.; Rooijakkers, S.H.
Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes
BMC Biol.
13
93
2015
Homo sapiens
brenda
Heesterbeek, D.; Bardoel, B.; Parsons, E.; Bennett, I.; Ruyken, M.; Doorduijn, D.; Gorham, R.J.; Berends, E.; Pyne, A.; Hoogenboom, B.; Rooijakkers, S.
Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases
EMBO J.
38
e99852
2019
Homo sapiens
brenda
Zwarthoff, S.A.; Berends, E.T.M.; Mol, S.; Ruyken, M.; Aerts, P.C.; Jozsi, M.; de Haas, C.J.C.; Rooijakkers, S.H.M.; Gorham, R.D.
Functional characterization of alternative and classical pathway C3/C5 convertase activity and inhibition using purified models
Front. Immunol.
9
1691
2018
Homo sapiens
brenda
Fridkis-Hareli, M.; Storek, M.; Or, E.; Altman, R.; Katti, S.; Sun, F.; Peng, T.; Hunter, J.; Johnson, K.; Wang, Y.; Lundberg, A.S.; Mehta, G.; Banda, N.K.; Michael Holers, V.
The human complement receptor type 2 (CR2)/CR1 fusion protein TT32, a novel targeted inhibitor of the classical and alternative pathway C3 convertases, prevents arthritis in active immunization and passive transfer mouse models
Mol. Immunol.
105
150-164
2019
Homo sapiens
brenda
Di Fede, M.; Biagini, M.; Cartocci, E.; Parillo, C.; Greco, A.; Martinelli, M.; Marchi, S.; Pezzicoli, A.; Delany, I.; Rossi Paccani, S.
Neisseria heparin binding antigen is targeted by the human alternative pathway C3-convertase
PLoS ONE
13
e0194662
2018
Homo sapiens
brenda
Pisarenka, S.; Meyer, N.C.; Xiao, X.; Goodfellow, R.; Nester, C.M.; Zhang, Y.; Smith, R.J.H.
Modeling C3 glomerulopathies C3 convertase regulation on an extracellular matrix surface
Front. Immunol.
13
1073802
2022
Homo sapiens
brenda
Pedersen, H.; Jensen, R.K.; Jensen, J.M.B.; Fox, R.; Pedersen, D.V.; Olesen, H.G.; Hansen, A.G.; Christiansen, D.; Mazarakis, S.M.M.; Lojek, N.; Hansen, P.; Gadeberg, T.A.F.; Zarantonello, A.; Laursen, N.S.; Mollnes, T.E.; Johnson, M.B.; Stevens, B.; Thiel, S.; Andersen, G.R.
A complement C3-specific nanobody for modulation of the alternative cascade identifies the C-terminal domain of C3b as functional in C5 convertase activity
J. Immunol.
205
2287-2300
2020
Homo sapiens
brenda
Michels, M.A.H.M.; Maas, R.J.F.; van der Velden, T.J.A.M.; van de Kar, N.C.A.J.; van den Heuvel, L.P.W.J.; Volokhina, E.B.; Volokhina, E.B.
The role of properdin in C5 convertase activity and C5b-9 formation in the complement alternative pathway
J. Immunol.
207
2465-2472
2021
Homo sapiens
brenda
Hew, B.E.; Pangburn, M.K.; Vogel, C.W.; Fritzinger, D.C.
Identification of intermolecular bonds between human factor B and Cobra Venom Factor important for C3 convertase stability
Toxicon
184
68-77
2020
Naja sp.
brenda
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