PDBsum entry 4id5

Transferase/transferase inhibitor

PDB id: 4id5

Contents

Protein chains

556 a.a.

412 a.a.

Ligands

T27

DMS ×17

1FF

Metals

_MG

Waters ×889

References listed in PDB file

Key reference

• Title: Detecting allosteric sites of HIV-1 reverse transcriptase by X-Ray crystallographic fragment screening.
• Authors: J.D.Bauman, D.Patel, C.Dharia, M.W.Fromer, S.Ahmed, Y.Frenkel, R.S.Vijayan, J.T.Eck, W.C.Ho, K.Das, A.J.Shatkin, E.Arnold.
• Ref.: J Med Chem, 2013, 56, 2738-2746. [DOI no: 10.1021/jm301271j]
• PubMed id: 23342998

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.