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Molecular modeling studies on the urease active site and the enzyme-catalyzed urea hydrolysis

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Summary

These studies are an attempt to gain better insight into the pharmacophore requirements of urease. On the basis of published information on this enzyme (EXAFS, amino acid sequence, essential groups at the active site) a hypothetical nickel-tripeptide complex, as preliminary substitute for the urease active site was modeled using computer-aided molecular modeling techniques. The results suggest two alternative docking modes of urea and reaction intermediates, corresponding to two different reaction mechanisms. Both binding modes are compatible with the docking of known potent inhibitors such as selected hydroxamic acids and phosphorodiamides. The results can be used to help in the design of new potential inhibitors of urease.

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Authors and Affiliations

  1. Lehrstuhl für Allgemeine Chemie und Biochemie der TU München, W-8050, Freising-Weihenstephan, Germany

    Ramiro Medina

  2. Central Research Units, F. Hoffmann-La Roche Ltd., CH-4002, Basel, Switzerland

    Klaus Müller

Authors
  1. Ramiro Medina
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  2. Klaus Müller
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Medina, R., Müller, K. Molecular modeling studies on the urease active site and the enzyme-catalyzed urea hydrolysis. J Computer-Aided Mol Des 4, 355–367 (1990). https://doi.org/10.1007/BF00117401

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  • DOI: https://doi.org/10.1007/BF00117401

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