The ketone cinnamoyl-(1-13C-Phe)-CGly-Pro-Pro is a tetrahedral transition state analog inhibitor of C. histolyticum collagenase |
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Authors: | D Grobelny C Teater R E Galardy |
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Institution: | Department of Biochemistry, University of Kentucky, Lexington 40536. |
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Abstract: | 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. |
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