The ketone cinnamoyl-(1-13C-Phe)-CGly-Pro-Pro is a tetrahedral transition state analog inhibitor of C. histolyticum collagenase.
The ketone cinnamoyl-(1-13C-Phe)-CGly-Pro-Pro [(4-13C-5-cinnamido-4-oxo-6-phenylhexanoyl)-Pro-Pro 2] competitively inhibits a mixture of collagenases from Clostridium histolyticum with a Ki of 40 +/- 6 nM. 13C-nmr spectroscopy of the ketone in the presence of this collagenase shows a bound 13C resonance at 102.6 ppm and the resonance of the free ketone at 212 ppm. Ketone alone shows no trace (less than 0.5%) of a resonance in the region around 100 ppm. The bound resonance is displaceable by another competitive inhibitor. This ketone is thus a transition state analog which is rehybridized from trigonal planar to tetrahedral upon binding to collagenase.
Grobelny
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Department of Biochemistry, University of Kentucky, Lexington 40536.
Teater
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Galardy
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D001665:Binding Sites; D001667:Binding, Competitive; D003013:Clostridium / Q000201:enzymology*; D004151:Dipeptides / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D007700:Kinetics; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004151:Dipeptides; D007659:Ketones; C058832:cinnamido-2-methyl-5-oxoheptanoyl-prolyl-arginine; C058831:(5-cinnamido-4-oxo-6-phenylhexanoyl)prolyl-proline; D003012:Microbial Collagenase