Effects of zinc on factor I cofactor activity of C4b-binding protein and factor H.

Article Details

Citation

Blom AM, Kask L, Ramesh B, Hillarp A

Effects of zinc on factor I cofactor activity of C4b-binding protein and factor H.

Arch Biochem Biophys. 2003 Oct 15;418(2):108-18.

PubMed ID
14522582 [ View in PubMed
]
Abstract

Complement inhibition is to a large extent achieved by proteolytic degradation of activated complement factors C3b and C4b by factor I (FI). This reaction requires a cofactor protein that binds C3b/C4b. We found that the cofactor activity of C4b-binding protein towards C4b/C3b and factor H towards C3b increase at micromolar concentrations of Zn(2+) and are abolished at 2 mM Zn(2+) and above. 65Zn(2+) bound to C3b and C4b molecules but not the cofactors or FI when they were immobilized in a native form on a nitrocellulose membrane. Zn(2+) binding constants for C3met (0.2 microM) and C4met (0.1 microM) were determined using fluorescent chelator. It appears that higher cofactor activity at low zinc concentrations is due to an increase of affinity between C4b/C3b and cofactor proteins as assessed by surface plasmon resonance. Inhibition of the reaction seen at higher concentrations is due to aggregation of C4b/C3b.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ZincC4b-binding protein alpha chainProteinHumans
Unknown
Not AvailableDetails
ZincC4b-binding protein beta chainProteinHumans
Unknown
Not AvailableDetails
ZincComplement C4-BProteinHumans
Unknown
Not AvailableDetails
Zinc acetateC4b-binding protein alpha chainProteinHumans
Unknown
Not AvailableDetails
Zinc acetateC4b-binding protein beta chainProteinHumans
Unknown
Not AvailableDetails
Zinc acetateComplement C4-BProteinHumans
Unknown
Not AvailableDetails
Zinc chlorideC4b-binding protein alpha chainProteinHumans
Unknown
Modulator
Details
Zinc chlorideC4b-binding protein beta chainProteinHumans
Unknown
Modulator
Details
Zinc chlorideComplement C4-BProteinHumans
Unknown
Modulator
Details
Zinc sulfate, unspecified formC4b-binding protein alpha chainProteinHumans
Unknown
Modulator
Details
Zinc sulfate, unspecified formC4b-binding protein beta chainProteinHumans
Unknown
Modulator
Details
Zinc sulfate, unspecified formComplement C4-BProteinHumans
Unknown
Modulator
Details