Modelling transition state analogues and enzyme-inhibitor complexes of zinc-containing class II aldolases and metalloproteases |
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Authors: | M. Ruf K. Weis I. Brasack H. Vahrenkamp |
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Affiliation: | Institut für Anorganische und Analytische Chemie der Universität Freiburg, Albertstrasse 21, D-79104, Frieburg, Germany |
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Abstract: | The zinc complex Tp*Zn---OH (1:Tp* = hydrotris-(3-cumyl,5-methyl-pyrazolyl)borate) which is a model of hydrolytic zinc enzymes was reacted with hydroxamic acids and hydroxyketones. Two hydroxamates Tp*Zn-Hya (2: Hya = acetohydroxamate, 3: Hya = 2-hydroxamato-4-methylpentanoyl-alanyl-glycylamide) and two ketoalcoholates Tp*Zn-Kea (4: Kea = hydroxyacetonate, 5: Kea = cumoylacetonate) were obtained. Crystal structure determinations of 2, 3 and 5 have revealed distorted ZnN3O2 coordinations in each case. The immediate environment of the zinc ion in the hydroxamates closely resembles that in enzyme-(hydroxamate)inhibitor complexes of zinc-containing metalloproteases like collagenases and thermolysin or of class II aldolases like fuculose-1-phoshate aldolase. Like in the enzymes the hydroxamates and the ketoalcoholates can serve as transition state analogues of the enzyme-catalysed reactions. |
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Keywords: | Crystal structures Zinc complexes Hydroxamate complexes Ketoalcoholate complexes Metalloenzyme-inhibitor modelling |
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