Three-dimensional structural model analysis of the binding site of lithocholic acid, an inhibitor of DNA polymerase beta and DNA topoisomerase II.
J Biochem
; 130(5): 657-64, 2001 Nov.
Article
en En
| MEDLINE
| ID: mdl-11686928
The molecular action of lithocholic acid (LCA), a selective inhibitor of mammalian DNA polymerase beta (pol beta), was investigated. We found that LCA could also strongly inhibit the activity of human DNA topoisomerase II (topo II). No other DNA metabolic enzymes tested were affected by LCA. Therefore, LCA should be classified as an inhibitor of both pol beta and topo II. Here, we report the molecular interaction of LCA with pol beta and topo II. By three-dimensional structural model analysis and by comparison with the spatial positioning of specific amino acids binding to LCA on pol beta (Lys60, Leu77, and Thr79), we obtained supplementary information that allowed us to build a structural model of topo II. Modeling analysis revealed that the LCA-interaction interface in both enzymes has a pocket comprised of three amino acids in common, which binds to the LCA molecule. In topo II, the three amino acid residues were Lys720, Leu760, and Thr791. These results suggested that the LCA binding domains of pol beta and topo II are three-dimensionally very similar.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN-Topoisomerasas de Tipo II
/
ADN Polimerasa beta
/
Ácido Litocólico
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biochem
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido