RNase, enzyme-inhibitor complexes

Combined with a difference technique the method results in substantial simplifications of the complex protein nmr spectra and in an effective increase in the spectral resolution for the polarized groups. This permits detailed studies of various interactions of proteins, such as the enzyme-inhibitor interactions discussed in sections 5,2 and 6.2 for RNase A and lysozyme. For both enzymes the photo-CIDNP spectrum proved to be very sensitive to the presence of inhibitors, albeit in conpletely different ways Examples of applications to the study of protein-nucleic acid interactions will be treated by Hilbers et al. elsewhere in this volume. We believe that in spite of its brief existence the photo-CIDNP method is potentially a powerful tool for the study of protein structure in solution. 

An example of enzyme depletion is the ribonuclease inhibitor isolated from human placenta by Blackburn, Wilson Moore. This protein forms a 1 1 complex with bovine pancreatic RNase A and is a noncompetitive... 

Reverse transcriptase (RT) plays a critical role in the early steps of the life of human immunodeficiency virus (HIV) (304), and for over a decade has been one of the major targets of AIDS therapy. Polycitone A (280) was found to be a potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerases (305). Polycitone A exhibited potent inhibitory capacity of both RNA- and DNA-directed DNA polymerases. It inhibits retroviral reverse transcriptases (RTs) of human immunodeficiency virus type 1 (HIV), murine leukemia virus (MLV) and mouse mammary tumor virus (MMTV)] as efficiently as cellular DNA polymerases of both DNA polymerases a and p and the prokaryotic Klenow fragment of Escherichia coli DNA polymerase I. The mode and mechanism of inhibition of the DNA-polymerase activity associated with HIV-1 RT by polycitone A (280) have been studied. The results suggest that the inhibitory capacity of the DNA polymerase activity is independent of the template-primer used. The RNase H function is hardly affected by this inhibitor. Polycitone A has been shown to interfere with DNA primer extension, as well as with the formation of the RT-DNA complex. Steady-state kinetic studies demonstrate that this inhibitor can be considered as an allosteric inhibitor of HIV-1 RT. The target site on the enzyme may be also spatially related to the... 

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