3ZSQ

Small molecule inhibitors of the LEDGF site of HIV type 1 integrase identified by fragment screening and structure based drug design

3ZSQ の概要

• エントリーDOI: 10.2210/pdb3zsq/pdb
• 関連するPDBエントリー: 1HYV 1HYZ 3ZSO 3ZSR 3ZSV 3ZSW 3ZSX 3ZSY 3ZSZ 3ZT0 3ZT1 3ZT2 3ZT3 3ZT4
• 分子名称: INTEGRASE, SULFATE ION, ACETIC ACID, ... (6 entities in total)
• 機能のキーワード: transferase, aids
• 由来する生物種: HUMAN IMMUNODEFICIENCY VIRUS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38509.41

構造登録者

Peat, T.S.,Newman, J.,Rhodes, D.I.,Vandergraaff, N.,Le, G.,Jones, E.D.,Smith, J.A.,Coates, J.A.V.,Thienthong, N.,Dolezal, O.,Ryan, J.H.,Savage, G.P.,Francis, C.L.,Deadman, J.J. (登録日: 2011-06-30, 公開日: 2012-07-11, 最終更新日: 2023-12-20)

主引用文献

Peat, T.S.,Rhodes, D.I.,Vandegraaff, N.,Le, G.,Smith, J.A.,Clark, L.J.,Jones, E.D.,Coates, J.A.V.,Thienthong, N.,Newman, J.,Dolezal, O.,Mulder, R.,Ryan, J.H.,Savage, G.P.,Francis, C.L.,Deadman, J.J.
Small Molecule Inhibitors of the Ledgf Site of Human Immunodeficiency Virus Integrase Identified by Fragment Screening and Structure Based Design.
Plos One, 7:40147-, 2012

PubMed Abstract: A fragment-based screen against human immunodeficiency virus type 1 (HIV) integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF) binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.

PubMed: 22808106
DOI: 10.1371/JOURNAL.PONE.0040147

実験手法

X-RAY DIFFRACTION (1.7 Å)