公开(公告)号：EP2455397A1

公开(公告)日：2012-05-23

申请号：EP10799831.2

申请日：2010-07-13

申请人： National University Corporation Kobe University ,  Japan Synchrotron Radiation Research Institute

发明人： KATAOKA, Tohru ,  SHIMA, Fumi ,  TAMURA, Atsuo ,  KUMASAKA, Takashi

IPC分类号： C07K14/82 ,  C12N15/09 ,  C30B7/04 ,  C30B29/58 ,  G01N33/15 ,  G01N33/50

CPC分类号： C07K14/82 ,  C07K2299/00 ,  C30B7/00 ,  C30B29/58 ,  G01N33/566 ,  G01N2333/4719 ,  G01N2500/02

摘要： An object of the present invention is to provide a co-crystal of a Ras polypeptide which adopts a conformation having a pocket on the molecular surface of Ras and GTP or a GTP analog, a production method for the crystal, and a screening method for a Ras function inhibitor based on information about the conformation obtained by X-ray crystallographic analysis using the crystal. The object is achieved by focusing on a mutation which adopts a conformation having a pocket on the molecular surface of Ras, acquiring a mutant Ras polypeptide having introduced therein such mutation, producing a co-crystal of the mutant Ras polypeptide and a GTP analog, and further subjecting the co-crystal to X-ray crystallographic analysis to acquire structural information about the conformation including information about the structure surrounding the pocket.

摘要翻译： 本发明的目的是提供一种Ras多肽的共晶，其采用在Ras和GTP的分子表面上具有口袋的构象或GTP类似物，晶体的制备方法和用于 基于通过使用晶体的X射线晶体学分析获得的关于构象的信息的Ras功能抑制剂。 该目的通过聚焦在Ras分子表面上具有口袋构象的突变来实现，获得在其中引入了这种突变的突变型Ras多肽，产生突变型Ras多肽和GTP类似物的共晶体，以及 进一步对共晶进行X射线晶体学分析以获得关于构象的结构信息，包括关于口袋周围结构的信息。