Literature summary for 2.7.7.49 extracted from

Hang, J.Q.; Li, Y.; Yang, Y.; Cammack, N.; Mirzadegan, T.; Klumpp, K.
Substrate-dependent inhibition or stimulation of HIV RNase H activity by non-nucleoside reverse transcriptase inhibitors (NNRTIs) (2007), Biochem. Biophys. Res. Commun., 352, 341-350.

Protein Variants

Protein Variants	Comment	Organism
K103N	mutation shows only moderate effects on either polymerase or RNAse H inhibitory potencies of GW8248 and TMC-125. IC50 for nevirapine is strongly enhanced. 1.6fold decrease in IC50-value for capravirine, 18.8fold increase in IC50-value for efavirenz	Human immunodeficiency virus 1
K103N/Y181C	mutation shows only moderate effects on either polymerase or RNAse H inhibitory potencies of GW8248 and TMC-125. IC50 for nevirapine is strongly enhanced. 1.3fold increase in IC50-value for capravirine, 21.8fold increase in IC50-value for efavirenz	Human immunodeficiency virus 1
Y181C	mutation shows only moderate effects on either polymerase or RNAse H inhibitory potencies of GW8248 and TMC-125. IC50 for nevirapine is strongly enhanced. 2.1fold increase in IC50-value for capravirine, IC50 for efavirenz is nearly identical to wild-type value	Human immunodeficiency virus 1
Y188L	mutation shows only moderate effects on either polymerase or RNAse H inhibitory potencies of GW8248 and TMC-125. IC50 for nevirapine is strongly enhanced. 47.8fold increase in IC50-value for capravirine, 58fold increase in IC50-value for efavirenz	Human immunodeficiency virus 1

Inhibitors

Inhibitors	Comment	Organism
capravirine	HIV reverse transcriptase contains two distinct protein domains catalyzing DNA polymerase and RNase H activities. Inhibits 5'-RNA directed HIV RNase H activity of reverse transcriptase. Potency of RNase H inhibition correlats with the respective potencies of DNA polymerase inhibition	Human immunodeficiency virus 1
efavirenz	HIV reverse transcriptase contains two distinct protein domains catalyzing DNA polymerase and RNase H activities. Inhibits 5'-RNA directed HIV RNase H activity of reverse transcriptase. Potency of RNase H inhibition correlats with the respective potencies of DNA polymerase inhibition	Human immunodeficiency virus 1
GW8248	HIV reverse transcriptase contains two distinct protein domains catalyzing DNA polymerase and RNase H activities. Inhibits 5'-RNA directed HIV RNase H activity of reverse transcriptase. Potency of RNase H inhibition correlats with the respective potencies of DNA polymerase inhibition	Human immunodeficiency virus 1
nevirapine	HIV reverse transcriptase contains two distinct protein domains catalyzing DNA polymerase and RNase H activities. Inhibits 5'-RNA directed HIV RNase H activity of reverse transcriptase. Potency of RNase H inhibition correlats with the respective potencies of DNA polymerase inhibition	Human immunodeficiency virus 1
TMC-125	HIV reverse transcriptase contains two distinct protein domains catalyzing DNA polymerase and RNase H activities. Inhibits 5'-RNA directed HIV RNase H activity of reverse transcriptase. Potency of RNase H inhibition correlats with the respective potencies of DNA polymerase inhibition	Human immunodeficiency virus 1

Organism

Organism	UniProt	Comment	Textmining
Human immunodeficiency virus 1	-	-	-

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.0000037	-	mutant enzyme Y181C	Human immunodeficiency virus 1	efavirenz
0.0000039	-	wild-type enzyme	Human immunodeficiency virus 1	efavirenz
0.0000046	-	mutant enzyme K103N	Human immunodeficiency virus 1	GW8248
0.0000051	-	mutant enzyme K103N/Y181C	Human immunodeficiency virus 1	GW8248
0.0000054	-	mutant enzyme K103N	Human immunodeficiency virus 1	capravirine
0.0000059	-	mutant enzyme Y181C	Human immunodeficiency virus 1	GW8248
0.0000082	-	wild-type enzyme	Human immunodeficiency virus 1	GW8248
0.0000086	-	wild-type enzyme	Human immunodeficiency virus 1	capravirine
0.0000112	-	mutant enzyme K103N/Y181C	Human immunodeficiency virus 1	capravirine
0.0000126	-	mutant enzyme K103N	Human immunodeficiency virus 1	TMC-125
0.0000183	-	mutant enzyme Y181C	Human immunodeficiency virus 1	capravirine
0.0000209	-	mutant enzyme Y181C	Human immunodeficiency virus 1	TMC-125
0.0000245	-	wild-type enzyme	Human immunodeficiency virus 1	TMC-125
0.0000324	-	mutant enzyme K103N/Y181C	Human immunodeficiency virus 1	TMC-125
0.0000647	-	mutant enzyme Y188L	Human immunodeficiency virus 1	TMC-125
0.0000679	-	mutant enzyme Y188L	Human immunodeficiency virus 1	GW8248
0.0000734	-	mutant enzyme K103N	Human immunodeficiency virus 1	efavirenz
0.0000849	-	mutant enzyme K103N/Y181C	Human immunodeficiency virus 1	efavirenz
0.000228	-	mutant enzyme Y188L	Human immunodeficiency virus 1	efavirenz
0.000411	-	mutant enzyme Y188L	Human immunodeficiency virus 1	capravirine
0.002217	-	wild-type enzyme	Human immunodeficiency virus 1	nevirapine