3QIN

Crystal Structure of HIV-1 RNase H p15 with engineered E. coli loop and pyrimidinol carboxylic acid inhibitor

Summary for 3QIN

• Entry DOI: 10.2210/pdb3qin/pdb
• Related: 3HYF
• Descriptor: Fusion protein of HIV-1 RNase H p15 with engineered E. coli loop, MANGANESE (II) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: rnase h, hiv-1, inhibitor, nuclease, transferase, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Human immunodeficiency virus type 1 group M subtype B (HIV-1); More
• Total number of polymer chains: 1
• Total formula weight: 17482.54

Authors

Lansdon, E.B.,Kirschberg, T.A. (deposition date: 2011-01-27, release date: 2011-04-20, Last modification date: 2023-09-13)

Primary citation

Lansdon, E.B.,Liu, Q.,Leavitt, S.A.,Balakrishnan, M.,Perry, J.K.,Lancaster-Moyer, C.,Kutty, N.,Liu, X.,Squires, N.H.,Watkins, W.J.,Kirschberg, T.A.
Structural and Binding Analysis of Pyrimidinol Carboxylic Acid and N-Hydroxy Quinazolinedione HIV-1 RNase H Inhibitors.
Antimicrob.Agents Chemother., 55:2905-2915, 2011

PubMed Abstract: HIV-1 RNase H breaks down the intermediate RNA-DNA hybrids during reverse transcription, requiring two divalent metal ions for activity. Pyrimidinol carboxylic acid and N-hydroxy quinazolinedione inhibitors were designed to coordinate the two metal ions in the active site of RNase H. High-resolution (1.4 Å to 2.1 Å) crystal structures were determined with the isolated RNase H domain and reverse transcriptase (RT), which permit accurate assessment of the metal and water environment at the active site. The geometry of the metal coordination suggests that the inhibitors mimic a substrate state prior to phosphodiester catalysis. Surface plasmon resonance studies confirm metal-dependent binding to RNase H and demonstrate that the inhibitors do not bind at the polymerase active site of RT. Additional evaluation of the RNase H site reveals an open protein surface with few additional interactions to optimize active-site inhibitors.

PubMed: 21464257
DOI: 10.1128/AAC.01594-10

Experimental method

X-RAY DIFFRACTION (1.6967 Å)