当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Molecular interaction model for the C1B domain of protein kinase C-gamma in the complex with its activator phorbol-12-myristate-13-acetate in water solution and lipid bilayer.

Molecular interaction model for the C1B domain of protein kinase C-gamma in the complex with its activator phorbol-12-myristate-13-acetate in water solution and lipid bilayer.

Abstract：

:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydrogen bonds, which are critical for the forming of the diacylglycerols/phorbol esters binding site, and indicates the important role of Gln27 for the geometry of this site. According to the model, PMA interacts with the C1B domain by hydrophobic interactions with Pro11 and Tyr22 and by three persistent hydrogen bonds between the C3 carbonyl group of PMA and Gly23 and between the C20 hydroxyl group of PMA and the Leu21 and Thr12 residues of the C1B domain. The C9 hydroxyl group of PMA does not interact with the C1B domain, but it is involved in the interaction with the DPPC bilayer. Two preferential orientations of the C1B-PMA complex toward the DPPC bilayer resulted from our molecular modeling study.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Hritz J,Ulicny J,Laaksonen A,Jancura D,Miskovsky P

doi

10.1021/jm049786s

keywords:

subject

Has Abstract

pub_date

2004-12-16 00:00:00

pages

6547-55

issue

26

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

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