3.4.21.43: classical-complement-pathway C3/C5 convertase
This is an abbreviated version!
For detailed information about classical-complement-pathway C3/C5 convertase, go to the full flat file.
Word Map on EC 3.4.21.43
Reaction
Selective cleavage of Arg-/-Ser bond in complement component C3 alpha-chain to form C3a and C3b, and Arg-/- bond in complement component C5 alpha-chain to form C5a and C5b =
Synonyms
C3 convertase, C3/C5 convertase, C3b 2 Bb, C3b2Bb, C3bBb, C3bBbP, C4, C423, C4b,2a, C4b,2a,3b, C4b,C2a, C4b2a, C4b2a(C3b)n, C4b2a3b, C4b2aC3b, C4bC2a, C5 convertase, classical C3 convertase, classical C5 convertase, classical pathway C3 convertase, classical pathway C3/C5 convertase, classical pathway C5 convertase, complement C3 convertase, CP C3 convertase, CP C3/C5 convertase, CP C5 convertase, EAC1,C4b,C2a, EC 3.4.21.44, high affinity C5 convertase, soluble C3 convertase, surface-bound C3 convertase
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3.4.21.43 classical-complement-pathway C3/C5 convertaseAdvanced search results
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Substrates Products on EC 3.4.21.43 - classical-complement-pathway C3/C5 convertase
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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
complement component C3 + H2O
?
-
classical pathway of the complement system
-
-
?
complement component C3 + H2O
component C3b + anaphylatoxin C3a
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-
iC3b is generated by Factor I after formation of C3b. iC3b is a proteolytically inactive form of C3b that retains the ability to opsonize microbes, but cannot participate in convertase function
-
?
complement component C5 + H2O
?
-
activity of enzyme bound to component C3b
-
-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
-
-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
-
-
-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
hydrolyzes peptide bond Arg77-Ser of the alpha-chain of C3
-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
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
-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
C3 complement cleavage is a central event in the activation of the complement system via the classical, the alternative, and the lectin pathway, overview
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-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
-
-
-
?
complement component C3 + H2O
complement component C3a + complement component C3b
-
-
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
-
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
hydrolyzes peptide bond Arg77 of the alpha-chain of complement component C5, cleavage of C5 requires complement fragment C3b which binds C5 and renders it susceptible to cleavage by the C4b,C2a complex
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
C5 convertases C4b2aC3b and C3b 2 Bb
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
C5 convertases, C4b2a3b and C3b2Bb, cleave C5 into the anaphylatoxin C5a and C5b followed by initiation of the terminal pathway, leading to formation of lytic C5b-9 membrane attack complexes, overview
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
C5 convertases, C4b2a3b and C3b2Bb, cleave C5 into the anaphylatoxin C5a and C5b, overview
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
-
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
-
-
-
?
complement component C5 + H2O
complement component C5a + complement component C5b
-
C5 convertases, C4b2a3b and C3b2Bb, cleave C5 into the anaphylatoxin C5a and C5b, overview
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-
?
complement componentC3 + H2O
complement component C3a + complement component C3b
-
C3 convertase C3bBb
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-
?
complement componentC3 + H2O
complement component C3a + complement component C3b
-
C3 convertases, C4b2a and C3bBb, cleave C3 into the anaphylatoxin C3a and C3b, overview
-
-
?
complement componentC3 + H2O
complement component C3a + complement component C3b
-
C3 convertases, C4b2a and C3bBb, cleave C3 into the anaphylatoxin C3a and C3b, overview
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-
?
additional information
?
-
-
dissociation of the classical-complement-pathway C3/C5 convertase by the regulators decay-accelerating factor, DAF, complement receptor 1, CR1, factor H and C4-binding protein C4BP, controls the function of the enzyme. Decay acceleration mediated by DAF, C4BP and CR1 requires interaction of the alpha4/5 region of C2a with a CCP2/CCP3 site of DAF or structurally homologous sites of CR1 and C4BP
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?
additional information
?
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-
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 C4b and increase the rate at which the catalytic subunit C2a is released into the medium. C2a loses its enzymatic activity and its ability to bind to C4b upon release. Although C4b is able to rebind C2 and reform the enzyme, the interaction with most decay-accelerating factors also leads to permanent proteolytic interaction of the cell-bound subunit C4b by a fluid-phase protease Factor I. Theses regulatory events limit cleavage of C3, reduce release of the anaphylatoxin C3a and control the formation of more efficient C5 convertase enzymes
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?
additional information
?
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-
factor B associates with complement component C3b and after proteolysis yields the C3 convertase of the alternative pathway, complement component C2A provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation, structural basis of the substrate specificity of the complement complex, overview, attachment of C3b to either C4b2a or C3bBb yields the C5 convertases, C4b2a3b and C3b2Bb, respectively, that cleave complement component C5
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-
?
additional information
?
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-
the alternative pathway lead via C3 convertase C3bBb and the C5 convertases C4b2aC3b and C3b 2 Bb
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-
?
additional information
?
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the C3 convertases, bimolecular complexes C4b2a and C3bBb, of the classical and alternative pathways are the central enzymes of the complement cascade, focused complement activation on foreign targets depends on regulatory proteins that decay the bimolecular C3 convertases, activity and regulation of complement control proteins CCP1-CCP4 as modules of the cell surface regulator, decay-accelerating factor, i.e. DAF or CD55, interaction of DAF with the convertases is mediated predominantly by two patches, one centered around Arg69 and Arg96 on CCP2 and the other around Phe148 and Leu171 on CCP3, structure, overview
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?
additional information
?
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the multi-domain serine protease C2 is the catalytic fragment of classical pathway C3 and C5 convertase of human complement of the classical and lectin pathways of complement activation, formation of these convertases requires the Mg2+-dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively, the C-terminal fragment C2a consisting of a serine protease and a von Willebrand factor type A domain, remains attached to C4b, forming the C3 convertase, C4b2a, structure, overview
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?
additional information
?
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the virion-associated Kaposis sarcoma-associated herpesvirus complement control protein is required for complement regulation and cell binding, involved structures, Kaposis sarcoma-associated herpesvirus, KSHV, encodes a lytic cycle protein called KSHV complement control protein, KCP, that inhibits activation of the complement cascade. It does so by regulating C3 convertases, accelerating their decay, and acting as a cofactor for factor I degradation of C4b and C3b, two components of the C3 and C5 convertases, KCP is expressed on the surface of human infected endothelial cells, mechanism, overview, K64Q/K65Q/K88Q KCP mutant lacks complement regulatory activity
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?
additional information
?
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pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury, overview
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?
additional information
?
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the enzyme catalyzes the central step of the complement cascade, overview, molecular interactions between MBL-associated serine protease-2, MASP-2, C4, and C2 and their activation fragments leading to complement activation via the lectin pathway, MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester, C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase C4b2a, overview
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?
