Elsevier

Methods in Enzymology

Volume 241, 1994, Pages 279-301
Methods in Enzymology

[15] Specificity of retroviral proteases: An analysis of viral and nonviral protein substrates

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Publisher Summary

This chapter focuses on current ideas regarding the specificity of the HIV protease and retroviral enzymes. It tries to identify a substrate of the HIV protease that has a well-defined tertiary structure where one can have confidence that the structure clearly relates to the conformation recognized by the protease. The retroviral enzymes require a long stretch of structure in a substrate that is accessible and of the “right” sequence and that is either extended or extendable as a consequence of binding to the enzyme. Such regions will most likely be found in interdomain segments akin to those linking the individual protein components of viral polyproteins. HIV protease will degrade some proteins extensively only when those proteins begin to lose their structural organization, thus the retroviral enzymes are sensors of structural integrity in their protein substrates. Structural proteins, proteins with acid-rich domains, proteins that begin to unfold by pH denaturation, and proteins from which tight-binding and structure-stabilizing ligands have been removed are ready targets for these enzymes.

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