4BE1

PFV intasome with inhibitor XZ-116

4BE1 の概要

• エントリーDOI: 10.2210/pdb4be1/pdb
• 関連するPDBエントリー: 2X6N 2X6S 2X74 2X78 4BAC 4BDY 4BDZ 4BE0 4BE2
• 分子名称: INTEGRASE, 19 NUCLEOTIDE PREPROCESSED PFV DONOR DNA (NON-TRANSFERRED STRAND), 17 NUCLEOTIDE PREPROCESSED PFV DONOR DNA (TRANSFERRED STRAND), ... (10 entities in total)
• 機能のキーワード: transferase-dna complex, protein-dna complex, dna integration, endonuclease, metal-binding, multifunctional enzyme, nuclease, nucleotidyltransferase, transferase, viral nucleoprotein, virion, dna-binding, zinc binding, hhcc motif, viral protein, recombination, inhibitor, recombination-inhibitor-dna complex, transferase/dna
• 由来する生物種: HUMAN SPUMARETROVIRUS; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 101064.21

構造登録者

Hare, S.,Cherepanov, P. (登録日: 2012-10-08, 公開日: 2012-10-31, 最終更新日: 2023-12-20)

主引用文献

Metifiot, M.,Maddali, K.,Johnson, B.C.,Hare, S.,Smith, S.J.,Zhao, X.Z.,Marchand, C.,Burke, T.R.,Hughes, S.H.,Cherepanov, P.,Pommier, Y.
Activities, Crystal Structures and Molecular Dynamics of Dihydro-1H-Isoindole Derivatives, Inhibitors of HIV-1 Integrase.
Acs Chem.Biol., 8:209-, 2013

PubMed Abstract: On the basis of a series of lactam and phthalimide derivatives that inhibit HIV-1 integrase, we developed a new molecule, XZ-259, with biochemical and antiviral activities comparable to raltegravir. We determined the crystal structures of XZ-259 and four other derivatives in complex with the prototype foamy virus intasome. The compounds bind at the integrase-Mg(2+)-DNA interface of the integrase active site. In biochemical and antiviral assays, XZ-259 inhibits raltegravir-resistant HIV-1 integrases harboring the Y143R mutation. Molecular modeling is also presented suggesting that XZ-259 can bind in the HIV-1 intasome with its dimethyl sulfonamide group adopting two opposite orientations. Molecular dynamics analyses of the HIV-1 intasome highlight the importance of the viral DNA in drug potency.

PubMed: 23075516
DOI: 10.1021/CB300471N

実験手法

X-RAY DIFFRACTION (2.71 Å)