1996
DOI: 10.1021/jm960056x
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Abstract: Crystal structures of HIV-1 reverse transcriptase (RT) complexed with a range of chemically diverse non-nucleoside inhibitors (NNIs) have shown a single pocket in which the inhibitors bind and details of the inhibitor-protein interactions. To delineate the structural requirements for an effective inhibitor, we have determined the structures of three closely related NNIs which vary widely in their potencies. Crystal structures of HIV-1 RT complexed with two very potent inhibitors, MKC-442 and TNK-651, at 2.55 a… Show more

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Cited by 332 publications
(396 citation statements)
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“…Some data were collected using rotating-anode sources (and an experimental setup similar to that described above), but, due to the weak diffraction from these crystals, the majority of data were collected at synchrotron sources. The experimental setups have been described previously (Ren, Esnouf, Garman et al, 1995;Esnouf et al, 1995, 1997: Ren, Esnouf, Hopkins et al, 1995Hopkins et al, 1996). Nearly 1000 crystals have been examined, but most do not show high-resolution diffraction from single lattices.…”
Section: Methodsmentioning
confidence: 99%
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“…Some data were collected using rotating-anode sources (and an experimental setup similar to that described above), but, due to the weak diffraction from these crystals, the majority of data were collected at synchrotron sources. The experimental setups have been described previously (Ren, Esnouf, Garman et al, 1995;Esnouf et al, 1995, 1997: Ren, Esnouf, Hopkins et al, 1995Hopkins et al, 1996). Nearly 1000 crystals have been examined, but most do not show high-resolution diffraction from single lattices.…”
Section: Methodsmentioning
confidence: 99%
“…7 Data collection and structure refinement for the complexes in cell forms C to F have been described previously (Ren, Esnouf, Garman et al, 1995;Ren, Esnouf, Hopkins et al, 1995;Hopkins et al, 1996). Details of the collection and processing of data from cell forms A and B will be described elsewhere.…”
Section: Number Of Residues Contributing To Each Crystal Contact Contmentioning
confidence: 99%
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“…Subsequent structures of the enzyme with a number of different NNRTIs bound have demonstrated that these inhibitors bind to the same pocket, with only minor differences in protein conformation, and substantially overlap the site occupied by nevirapine (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Comparison of these structures with those of the apoenzyme shows that the NNRTI-binding pocket is induced upon NNRTI binding (21)(22)(23)(24).…”
mentioning
confidence: 99%
“…The chemotherapeutic e cacy of pyrimidine-related derivatives is related to their ability to inhibit vital enzymes responsible for DNA biosynthesis including dihydrofolate reductase (DHFR), thymidylate synthetase (TSase), thymidine phosphorylase (TPase) and reverse transcriptase (RTase). 1-[2-(Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and its derivatives have long been known for their potent activity against human immunode ciency viruses (HIV) [1][2][3][4][5][6][7]. In addition, numerous pyrimidine-related derivatives displayed marked activities against herpes simplex viruses (HSV) [8], and hepatitis B viruses (HBV) [9].…”
Section: Discussionmentioning
confidence: 99%