Summary for 4KFB
| Entry DOI | 10.2210/pdb4kfb/pdb |
| Descriptor | REVERSE TRANSCRIPTASE/RIBONUCLEASE H, EXORIBONUCLEA P66 RT, P51 RT, ethyl pyrazolo[1,5-a]pyridine-3-carboxylate, ... (6 entities in total) |
| Functional Keywords | rna-directed dna polymerase, dna polymerase, endonuclease, hydrolase, multifunctional enzyme, hydrolase-inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) More |
| Cellular location | Gag-Pol polyprotein: Host cell membrane; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03366 P03366 |
| Total number of polymer chains | 2 |
| Total formula weight | 115423.72 |
| Authors | Bauman, J.D.,Patel, D.,Arnold, E. (deposition date: 2013-04-26, release date: 2013-05-15, Last modification date: 2024-02-28) |
| Primary citation | Bauman, J.D.,Patel, D.,Dharia, C.,Fromer, M.W.,Ahmed, S.,Frenkel, Y.,Vijayan, R.S.,Eck, J.T.,Ho, W.C.,Das, K.,Shatkin, A.J.,Arnold, E. Detecting Allosteric Sites of HIV-1 Reverse Transcriptase by X-Ray Crystallographic Fragment Screening. J.Med.Chem., 56:2738-, 2013 Cited by PubMed Abstract: HIV-1 reverse transcriptase (RT) undergoes a series of conformational changes during viral replication and is a central target for antiretroviral therapy. The intrinsic flexibility of RT can provide novel allosteric sites for inhibition. Crystals of RT that diffract X-rays to better than 2 Å resolution facilitated the probing of RT for new druggable sites using fragment screening by X-ray crystallography. A total of 775 fragments were grouped into 143 cocktails, which were soaked into crystals of RT in complex with the non-nucleoside drug rilpivirine (TMC278). Seven new sites were discovered, including the Incoming Nucleotide Binding, Knuckles, NNRTI Adjacent, and 399 sites, located in the polymerase region of RT, and the 428, RNase H Primer Grip Adjacent, and 507 sites, located in the RNase H region. Three of these sites (Knuckles, NNRTI Adjacent, and Incoming Nucleotide Binding) are inhibitory and provide opportunities for discovery of new anti-AIDS drugs. PubMed: 23342998DOI: 10.1021/JM301271J PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.854 Å) |
Structure validation
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