Partial identification of the Zn2+-binding sites in factor XII and its activation derivatives.

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Rojkaer R, Schousboe I

Partial identification of the Zn2+-binding sites in factor XII and its activation derivatives.

Eur J Biochem. 1997 Jul 15;247(2):491-6.

PubMed ID

9266689 [ View in PubMed

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Abstract

With the purpose of identifying the Zn2+-binding sites in factor XII, the effect of chemical modification of His, Glu and Asp residues, amino acids known to participate in the catalytic coordination binding of Zn2+ in a number of Zn2+-binding proteins, was analysed. The number of modifiable His residues in factor XII and alpha-factor XIIa was 16.0+/-0.7 and 17.3+/-0.7, respectively. When factor XII/alpha-factor XIIa was incubated with saturating concentrations of Zn2+ before the diethylpyrocarbonate modification of the His residues, these numbers were reduced to 6.3+/-0.1 and 8.21+/-0.5, indicating that ten and nine His residues, respectively, are involved in the binding. Analysis of the Zn2+-binding capacity of factor XII, alpha-factor XIIa and beta-factor XIIa showed that while factor XII contains four Zn2+-binding sites, alpha-factor XIIa had only three and beta-factor XIIa had none. Modification of the His residues resulted in a complete loss of Zn2+-binding while Asp/Glu modification resulted in loss of two and one Zn2+-binding sites in factor XII and alpha-factor XIIa, respectively. This suggests that two of the four sites in factor XII contain His residues, exclusively, while the two others are comprised of two His residues and one Asp/Glu residue. One of the latter is lost when factor XII is activated to alpha-factor XIIa. Two of the sites are suggested to be located at positions His40-His44 and His78-His82. The location of the remaining two sites are reduced to four possible positions.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Zinc	Coagulation factor XII	Protein	Humans	Unknown	Not Available	Details
Zinc acetate	Coagulation factor XII	Protein	Humans	Unknown	Not Available	Details