A predicted tertiary structure of a thrombin inhibitor-trypsin complex explains the mechanisms of the selective inhibition of thrombin, factor Xa, plasmin, and trypsin.
The tertiary structure of a thrombin inhibitor-trypsin complex has been predicted by a molecular modelling considering the van der Waals interactions between the inhibitor and the enzyme. The selective inhibition of trypsin, thrombin, factor Xa, and plasmin exhibited by arginine and lysine derivatives has been clearly explained based on the predicted structure and the homology in the amino acid sequences of these enzymes. The differences in the amino acid sequences at the positions corresponding to Ile63, Leu99, and Ser190 of trypsin give each enzyme different binding affinities toward inhibitors and result in the selective inhibition. The X-ray analysis of the inhibitor-trypsin complex is in progress to prove the predicted structure.
Matsuzaki
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T
Research Center, Mitsubishi Chemical Industries, Ltd., Kanagawa.
Sasaki
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C
Umeyama
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H
D000595:Amino Acid Sequence; D001665:Binding Sites; D015951:Factor Xa; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006801:Humans; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors
D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D013917:Thrombin; D015951:Factor Xa; D005341:Fibrinolysin