5CYQ

HIV-1 reverse transcriptase complexed with 4-bromopyrazole

Summary for 5CYQ

• Entry DOI: 10.2210/pdb5cyq/pdb
• Related: 5CW1 5CXR 5CYM
• Descriptor: HIV-1 reverse transcriptase, p66 subunit, HIV-1 reverse transcriptase, p51 subunit, 4-{[4-({4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile, ... (7 entities in total)
• Functional Keywords: 4-bromopyrazole, phasing, influenza endonuclease, fragment screening, transferase
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (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: 117620.78

Authors

Bauman, J.D.,Arnold, E. (deposition date: 2015-07-30, release date: 2015-12-30, Last modification date: 2023-09-27)

Primary citation

Bauman, J.D.,Harrison, J.J.,Arnold, E.
Rapid experimental SAD phasing and hot-spot identification with halogenated fragments.
IUCrJ, 3:51-60, 2016

PubMed Abstract: Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a 'magic bullet' that is capable of binding at many of the ligand 'hot spots' found in HIV-1 reverse transcriptase (RT). The binding locations can be in pockets that are 'hidden' in the unliganded crystal form, allowing rapid identification of these sites for in silico screening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K) by single-wavelength anomalous dispersion (SAD) from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.

PubMed: 26870381
DOI: 10.1107/S2052252515021259

Experimental method

X-RAY DIFFRACTION (2.147 Å)