3ZT0

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

Summary for 3ZT0

• Entry DOI: 10.2210/pdb3zt0/pdb
• Related: 1HYV 1HYZ 3ZSO 3ZSQ 3ZSR 3ZSV 3ZSW 3ZSX 3ZSY 3ZSZ 3ZT1 3ZT2 3ZT3 3ZT4
• Descriptor: INTEGRASE, SULFATE ION, (4-CARBOXY-1,3-BENZODIOXOL-5-YL)-N-{2-[(4-METHOXYBENZYL)CARBAMOYL]BENZYL}-N-METHYLMETHANAMINIUM, ... (4 entities in total)
• Functional Keywords: transferase, aids
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS
• Total number of polymer chains: 2
• Total formula weight: 38295.07

Authors

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. (deposition date: 2011-07-01, release date: 2012-07-11, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)