HIV-1 Reverse Transcriptase in Complex with Nevirapine: Difference between revisions
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== Conclusion == | == Conclusion == | ||
Analysis of the crystal structures of RT-DNA complexes in the presence and absence of nevirapine allows us to determine the effects of nonnucleosides on RT structure and function. Binding of nevirapine reveals several changes to the RT-DNA complex. It directly displaces the primer grip located in the palm subdomain, which causes the primer terminus to relocate, the thumb to lock in hyper-extension, decreased interaction between DNA and the polymerase domain, and distortion the dNTP binding site. As a result of the conformational changes nevirapine causes, the process of DNA synthesis by RT is essentially inhibited. Unfortunately, the high mutation rate caused by HIV-1 polymerase's low fidelity readily produces mutant strains that are resistant to NNRTIs. Understanding the precise mechanism of these compounds' inhibition is a key step in developing more effective drugs against HIV. | Analysis of the crystal structures of RT-DNA complexes in the presence and absence of nevirapine allows us to determine the effects of nonnucleosides on RT structure and function. Binding of nevirapine reveals several changes to the RT-DNA complex. It directly displaces the primer grip located in the palm subdomain, which causes the primer terminus to relocate, the thumb to lock in hyper-extension, decreased interaction between DNA and the polymerase domain, and distortion the dNTP binding site. As a result of the conformational changes nevirapine causes, the process of DNA synthesis by RT is essentially inhibited. Unfortunately, the high mutation rate caused by HIV-1 polymerase's low fidelity readily produces mutant strains that are resistant to NNRTIs. Understanding the precise mechanism of these compounds' inhibition is a key step in developing more effective drugs against HIV. | ||
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==References== | ==References== | ||
<references /> | <references /> | ||
