7KWU
Crystal Structure of HIV-1 RT in Complex with 16c (K07-15)
Summary for 7KWU
| Entry DOI | 10.2210/pdb7kwu/pdb |
| Descriptor | Reverse transcriptase p66, Reverse transcriptase p51, SULFATE ION, ... (7 entities in total) |
| Functional Keywords | human immunodeficiency virus 1, non nucleotide-reverse transcriptase inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Human immunodeficiency virus type 1 (HIV-1) More |
| Total number of polymer chains | 2 |
| Total formula weight | 115530.42 |
| Authors | Ruiz, F.X.,Arnold, E. (deposition date: 2020-12-02, release date: 2021-03-31, Last modification date: 2023-10-18) |
| Primary citation | Kang, D.,Ruiz, F.X.,Sun, Y.,Feng, D.,Jing, L.,Wang, Z.,Zhang, T.,Gao, S.,Sun, L.,De Clercq, E.,Pannecouque, C.,Arnold, E.,Zhan, P.,Liu, X. 2,4,5-Trisubstituted Pyrimidines as Potent HIV-1 NNRTIs: Rational Design, Synthesis, Activity Evaluation, and Crystallographic Studies. J.Med.Chem., 64:4239-4256, 2021 Cited by PubMed Abstract: There is an urgent unmet medical need for novel human immunodeficiency virus type 1 (HIV-1) inhibitors that are effective against a variety of NNRTI-resistance mutations. We report our research efforts aimed at discovering a novel chemotype of anti-HIV-1 agents with improved potency against a variety of NNRTI-resistance mutations in this paper. Structural modifications of the lead led to the identification of a potent inhibitor . yielded highly potent anti-HIV-1 activities and improved resistance profiles compared with the approved drug etravirine. The co-crystal structure revealed the key role of the water networks surrounding the NNIBP for binding and for resilience against resistance mutations, while suggesting further extension of toward the NNRTI-adjacent site as a lead development strategy. Furthermore, demonstrated favorable pharmacokinetic and safety properties, suggesting the potential of as a promising anti-HIV-1 drug candidate. PubMed: 33734714DOI: 10.1021/acs.jmedchem.1c00268 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.02 Å) |
Structure validation
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