The structure of docking domains in modular polyketide synthases

被引:177
作者
Broadhurst, RW [1 ]
Nietlispach, D [1 ]
Wheatcroft, MP [1 ]
Leadlay, PF [1 ]
Weissman, KJ [1 ]
机构
[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
来源
CHEMISTRY & BIOLOGY | 2003年 / 10卷 / 08期
关键词
D O I
10.1016/S1074-5521(03)00156-X
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
Polyketides from actinomycete bacteria provide the basis for many valuable medicines, so engineering genes for their biosynthesis to produce variant molecules holds promise for drug discovery. The modular polyketide synthases are particularly amenable to this approach, because each cycle of chain extension is catalyzed by a different module of enzymes, and the modules are arranged within giant multienzyme sub-units in the order in which they act. Protein-protein interactions between terminal docking domains of successive multienzymes promote their correct positioning within the assembly line, but because the overall complex is not stable in vitro, the key interactions have not been identified. We present here the NMR solution structure of a 120 residue polypeptide representing a typical pair of such domains, fused at their respective C and N termini: it adopts a stable dimeric structure which reveals the detailed role of these {predominantly helical} domains in docking and dimerization by modular polyketide synthases.
引用
收藏
页码:723 / 731
页数:9
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