Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome

被引：404

作者：

Groll, M

Berkers, CR

Ploegh, HL

Ovaa, H

机构：

[1] Univ Munich, Dept Physiol Chem, D-81377 Munich, Germany

[2] Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

STRUCTURE | 2006年 / 14卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.str.2005.11.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The dipeptide boronic acid bortezomib, also termed VELCADE (R), is a proteasome inhibitor now in use for the treatment of multiple myeloma, and its use for the treatment of other malignancies is being explored. We determined the crystal structure of the yeast 20S proteasome in complex with bortezomib to establish the specificity and binding mode of bortezomib to the proteasome's different catalytically active sites. This structure should enable the rational design of new boronic acid derivatives with improved affinities and specificities for individual active subunits.

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页码：451 / 456

页数：6

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