5UV5

Crystal Structure of a 2-Hydroxyisoquinoline-1,3-dione RNase H Active Site Inhibitor with Multiple Binding Modes to HIV Reverse Transcriptase

Summary for 5UV5

• Entry DOI: 10.2210/pdb5uv5/pdb
• Descriptor: Reverse transcriptase/ribonuclease H, p51 RT, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: reverse transcriptase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1); More
• Total number of polymer chains: 4
• Total formula weight: 229110.14

Authors

Kirby, K.A.,Sarafianos, S.G. (deposition date: 2017-02-19, release date: 2017-08-16, Last modification date: 2023-10-04)

Primary citation

Kirby, K.A.,Myshakina, N.A.,Christen, M.T.,Chen, Y.L.,Schmidt, H.A.,Huber, A.D.,Xi, Z.,Kim, S.,Rao, R.K.,Kramer, S.T.,Yang, Q.,Singh, K.,Parniak, M.A.,Wang, Z.,Ishima, R.,Sarafianos, S.G.
A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase.
Antimicrob. Agents Chemother., 61:-, 2017

PubMed Abstract: The RNase H (RNH) function of HIV-1 reverse transcriptase (RT) plays an essential part in the viral life cycle. We report the characterization of YLC2-155, a 2-hydroxyisoquinoline-1,3-dione (HID)-based active-site RNH inhibitor. YLC2-155 inhibits both polymerase (50% inhibitory concentration [IC] = 2.6 μM) and RNH functions (IC = 0.65 μM) of RT but is more effective against RNH. X-ray crystallography, nuclear magnetic resonance (NMR) analysis, and molecular modeling were used to show that YLC2-155 binds at the RNH-active site in multiple conformations.

PubMed: 28760905
DOI: 10.1128/AAC.01351-17

Experimental method

X-RAY DIFFRACTION (3 Å)