PB0324 - Probable Interaction of Protein Z Dependent Protease Inhibitor with Plasma Pre-kallikrein as Revealed by Phylogenetic Analyses

Background: Protein Z Dependent Protease Inhibitor (ZPI), a member of serpin super family, inhibits FXIa without the presence of procoagulants such as PZ, Calcium and Lipid membrane. Unlike other coagulation protease, FXI is a vitamin-k independent coagulation protein. FXI polypeptide is organised into four 90-91 amino acid repeats called apple domains designated as A1 to A4 from the N-terminus and a C-terminal protease domain. The plasma pre-kallikrein (PK), the precursor of protease plasma kallikrein (PKa) is the only other protein known to share this particular configuration. Also, the gene F11 that codes for FXI is duplicated from the gene KLKB1 that codes for PK.

Aims: We propose that ZPI might interact with PK as it is a FXI homolog and the gene (F11) codes for FXI and PK are orthologs. The current study is therefore aimed to probe the interaction between ZPI and PK.

Methods: Genome analyses of evolutionarily significant organisms, multiple sequence alignment analyses, phylogenetic tree construction, synteny analyses and molecular docking were used for the current study.

Results: It was observed that zebra fish genome consists of two genes homologous to KLKB1 in chromosome number 12 and 14. The pattern of branching in the phylogenetic tree constructed for Serpina10 orthologs and KLKB1 orthologs showed significant similarity. Docking pattern of PK from different organisms and the corresponding ZPI of those organisms also showed notable similarities.

Conclusion(s): Consequently, as the Serpina10 gene known to exist before the divergence of cartilaginous fish, ZPI should have a significant function other than anticoagulation by interacting with the predecessor protease of FXI and PK.