scholarly journals Effect of thiol compounds on human complement component C4

1993 ◽  
Vol 289 (3) ◽  
pp. 801-805 ◽  
Author(s):  
S Edmonds ◽  
A Gibb ◽  
E Sim
Keyword(s):  
Potent Inhibitor ◽  
Covalent Binding ◽  
Human Complement ◽  
Complement Protein ◽  
Inhibitory Potency ◽  
Thiol Compounds ◽  
Binding Reaction ◽  
Binding Surface ◽  
Hypertensive Drug ◽  
Human Complement Component

Thiol compounds have been investigated as inhibitors of the covalent binding reaction of human complement protein C4 using Sepharose-C1s as a combined activating and binding surface. o- and p-substituted aminothiophenols are equally effective inhibitors, whereas the m-substituted compound is a less potent inhibitor. The anti-hypertensive drug captopril is also shown to inhibit the covalent binding reaction. A comparison of the effects of these compounds on the covalent binding reaction of isolated C4A and C4B has been made. Results suggest that a Pro-to-Leu substitution in C4B is likely to account for the differences in inhibitory potency of C4B compared with C4A observed with the aromatic inhibitors.

scholarly journals The effect of residue 1106 on the thioester-mediated covalent binding reaction of human complement protein C4 and the monomeric rat α-macroglobulin α1 I3

FEBS Letters ◽  
1995 ◽  
Vol 368 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Xiang-Dong Ren ◽  
Alister W. Dodds ◽  
Jan J. Enghild ◽  
Charleen T. Chu ◽  
S.K. Alex Law
Keyword(s):  
Covalent Binding ◽  
Human Complement ◽  
Complement Protein ◽  
Binding Reaction

scholarly journals The covalent-binding reaction of complement component C3

1981 ◽  
Vol 193 (1) ◽  
pp. 115-127 ◽  
Author(s):  
R B Sim ◽  
T M Twose ◽  
D S Paterson ◽  
E Sim
Keyword(s):  
Ionic Strength ◽  
Covalent Binding ◽  
Limited Proteolysis ◽  
Life Time ◽  
Reactive Intermediate ◽  
Complement Protein ◽  
Binding Reaction ◽  
Complement Component C3 ◽  
Binding Surface ◽  
Nitrogen Nucleophiles

The complement protein C3, when activated by limited proteolysis, forms a short-lived reactive intermediate fragment, ‘nascent’ C3b, which is known to bind covalently to certain surfaces. The characteristics of the covalent binding reaction have been studied by using Sepharose-trypsin as a combined proteolytic activator and binding surface for C3. Binding of C3 to Sepharose-trypsin is saturable, with a maximum of 25-26 molecules of C3b bound per molecule of trypsin. A minimum life-time of about 60 microseconds for the reactive intermediate has been calculated from binding of C3 at saturation. Initial binding efficiencies of over 30% can be obtained at physiological pH and ionic strength. The efficiency of C3 binding to Sepharose-trypsin decreases as pH increases and also shows a slight decline at high ionic strength. The covalent binding of C3 to Sepharose-trypsin can be inhibited by a range of oxygen and nitrogen nucleophiles. Activation of C3 in the presence of radioactive forms of four such nucleophiles, phenylhydrazine, methylamine, glycerol and glucosamine results in apparent covalent incorporation of the nucleophile into the C3d fragment of C3. The quantity of radioactive nucleophile bound can be predicted from the observed potency of the nucleophile as an inhibitor of the binding of C3 to Sepharose-trypsin. The radioactive nucleophiles may be considered as ‘active-site’ labels for C3.

scholarly journals Non-enzymic activation of the covalent binding reaction of the complement protein C3

1983 ◽  
Vol 211 (2) ◽  
pp. 381-389 ◽  
Author(s):  
S K A Law
Keyword(s):  
Conformational Change ◽  
Hydroxy Group ◽  
Covalent Binding ◽  
Activation Mechanism ◽  
Complement Protein ◽  
Guanidinium Chloride ◽  
Cleavage Reaction ◽  
Binding Reaction ◽  
Physiological Conditions ◽  
Similar Dependence

The covalent binding of [3H]glycerol to C3 by the transfer of the acyl group of the internal thioester of C3 to the hydroxy group of glycerol can be activated either proteolytically by trypsin or by various chaotropes and denaturants. The activation of binding by trypsin or KBr showed similar dependence on the concentration of glycerol, indicating a similar activation mechanism. It is therefore concluded that the conformational change of the protein is the critical step in the binding reaction, and that the conversion of C3 into C3b under physiological conditions is only a means to induce the conformational change. Guanidinium chloride induces the binding of glycerol to C3 at concentrations of about 1 M. On increasing the concentration of guanidinium chloride the extent of binding declines and is accompanied by an increase in the autolytic cleavage reaction [Sim & Sim (1981) Biochem. J. 193, 129-141]. The autolytic cleavage reaction is therefore not independently activated with respect to the binding reaction. Its occurrence, however, is structurally restricted under physiological or limited denaturing conditions and is permissible only when C3 is brought to a higher denaturation state.

scholarly journals Inhibition of the covalent binding reaction of complement component C4 by penicillamine, an anti-rheumatic agent

1989 ◽  
Vol 259 (2) ◽  
pp. 415-419 ◽  
Author(s):  
E Sim ◽  
A W Dodds ◽  
A Goldin
Keyword(s):  
Immune Complex ◽  
Covalent Binding ◽  
Cysteine Residue ◽  
Complement Component ◽  
Complement Cascade ◽  
Class Iii ◽  
Thiol Compounds ◽  
Binding Reaction ◽  
Adverse Side Effects ◽  
Rate Of Reaction

D(-)-Penicillamine [D(-)-beta beta-dimethylcysteine] is an anti-arthritic drug, but its use is limited by adverse side effects, which include problems in immune-complex clearance. Complement is important as a source of inflammatory mediators in rheumatoid arthritis and is also involved in immune-complex clearance. Thus inhibition of the complement cascade would be likely to contribute to both the therapeutic and the toxic effects of penicillamine. It is shown that penicillamine and cysteine are potent inhibitors of the covalent binding of activated complement component C4 to immune complexes. [35S]Cysteine itself becomes covalently bound to C4b through the thioester site. Penicillamine and cysteine are more reactive with the C4A isotype than with the C4B isotype of the HLA class III protein C4. The limited amino acid sequence differences between C4A and C4B include a cysteine/serine interchange, and it is suggested that the cysteine residue in C4A contributes to the increased rate of reaction of C4A with the alpha-amino-beta-thiol compounds.

scholarly journals Covalent binding properties of the human complement protein C4 and hydrolysis rate of the internal thioester upon activation

1993 ◽  
Vol 2 (5) ◽  
pp. 706-716 ◽  
Author(s):  
Armin Sepp ◽  
Alister W. Dodds ◽  
Michael J. Anderson ◽  
R. Duncan Campbell ◽  
Antony C. Willis ◽  
...  
Keyword(s):  
Covalent Binding ◽  
Hydrolysis Rate ◽  
Human Complement ◽  
Complement Protein ◽  
Binding Properties

Binding reaction between the third human complement protein and small molecules

Biochemistry ◽  
1981 ◽  
Vol 20 (26) ◽  
pp. 7457-7463 ◽  
Author(s):  
Sai Kit A. Law ◽  
Tana M. Minich ◽  
R. P. Levine
Keyword(s):  
Small Molecules ◽  
Human Complement ◽  
Complement Protein ◽  
Binding Reaction ◽  
The Third
Sign in / Sign up

Export Citation Format

Share Document