Crystal Structures of Rhizopuspepsin/Inhibitor Complexes

  • Kevin D. Parris
  • Dennis J. Hoover
  • David R. Davies
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)


The crystal structures of the aspartic proteinases have been extensively studied over the past fifteen years (Hsu et al., 1977; Subramanian et al., 1977; reviewed by Davies, 1990). After the initial determinations of the native structures uncomplexed with inhibitors, a few complexes with pepstatin (Bott et al., 1982) and with a fragment of pepstatin (James et al., 1982) were reported. These studies showed that these inhibitors bound in the deep groove that separates the N- and C-terminal domains of the enzyme. Accompanying the binding of the inhibitor was a displacement of the “flap” region of the molecule, a hairpin loop that closes down on the inhibitor, the extent of the displacement depending on the initial location of the flap (James et al., 1982; Bott et al., 1982; Suguna et al., 1987 and Cooper et al., 1987). Since no other major conformational changes were observed, the crystals of these proteinases offered a convenient vehicle for examining a number of bound inhibitor conformations. Other factors facilitating the examination of these inhibitors were the availability of large numbers of renin inhibitors, and the fortunate ease of access to the combining site in several of the crystal forms, thus enabling the inhibitors to be soaked into the crystals.


Aspartic Proteinase Solvent Accessibility Renin Inhibitor Tetrahedral Intermediate Domain Rotation 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Kevin D. Parris
    • 1
  • Dennis J. Hoover
    • 2
  • David R. Davies
    • 1
  1. 1.Laboratory of Molecular BiologyNIDDK, NIHBethesdaUSA
  2. 2.Department of Medicinal Chemistry, Central Research DivisionPfizer IncGrotonUSA

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