The interaction of Staphylococcus aureus coagulase with prothrombin in various organisms

Research output: Types of ThesisMaster's thesisTheses


Staphylococcus aureus is a commensal bacterial pathogen in humans and it causes avariety of infectious diseases, from mild skin infections to life-threatening conditions. So-called ‘coagulase-positive’ S. aureus strains secrete an enzyme called coagulase thatactivates the central coagulation zymogen, prothrombin, without the usual proteolyticcleavage.

It has been found that coagulase cannot activate prothrombin of Mongolian gerbil, mouseor rat. The aim of this thesis was to examine the interaction between coagulase andprothrombin of different organisms, especially that of gerbil, mouse and rat.

This study involved amino acid sequence analysis of different organisms’ prothrombin anddetermining gerbil prothrombin sequence by means of PCR. Binding of coagulase toprothrombin of different species was determined using monoclonal anti-polyhistidine–agarose antibodies and studied by SDS PAGE. After determining the gene and proteinsequences for gerbil prothrombin, it was possible to construct three-dimensional models ofprothrombin-coagulase-complexes for gerbil and other organisms. The models of theprothrombin-coagulase complexes were built by the means of homology modeling, usingan available crystal structure of the human prothrombin-coagulase complex as a template.According to the sequence alignment, the coagulase-binding interface of prothrombin ishighly conserved and we could experimentally confirm that coagulase is able to bind to allof the reviewed organisms’ prothrombin. Instead, the homology models suggest that thereason why S. aureus coagulase cannot activate the rodents’ prothrombin is those subtlechanges in the prothrombin amino acid sequence that could interfere with the insertion ofcoagulase N-terminal residues into the zymogen’s catalytic site. 

Original languageUndefined/Unknown
Publication statusPublished - 2017
MoE publication typeG2 Master's thesis, polytechnic Master's thesis

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