Structure-function relationships in human alpha- and gamma-thrombins.
Human pro-coagulant alpha-thrombin may be proteolyzed under controlled conditions to the non-coagulant beta- and gamma-thrombin forms. These derivative forms nonetheless retain esterase and amidase activities with small substrates as well as several other thrombin functions. Structurally, human gamma-thrombin consists of three non-covalently associated fragments which retain structural integrity as measured by several spectroscopic criteria as well as enzymatic function. The protein folding characteristics of three-chain gamma-thrombin indicate that each fragment (domain) contains sufficient information to result in a correct renaturation of protein conformation. Those subtle structural differences which distinguish gamma- from alpha-thrombin are most likely the obstructions to fibrinogen binding which account for the loss of clotting activity.
D001665:Binding Sites; D004578:Electron Spin Resonance Spectroscopy; D006487:Hemostasis; D006801:Humans; D008958:Models, Molecular; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D011485:Protein Binding; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism*
D010446:Peptide Fragments; D013917:Thrombin