Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase
Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase
复制标题
DOI：
10.1016/j.chembiol.2007.07.012
复制
发表时间：
2007-08-01
影响因子：
--
通讯作者：
Khosla, Chaitan
中科院分区：
文献类型：
--
作者：
Tang, Yinyan;Chen, Alice Y.;Khosla, Chaitan
我们报告的2.6埃的X-射线晶体结构的190 kDa的同源二聚体片段从模块3的6-脱氧erthrone B合酶共价结合到抑制剂浅蓝菌素。该结构显示除了全长酮合酶（KS）和酰基转移酶（AT）结构域之外，还有两个组织良好的蛋白质间接头区域。KS结构域的底物结合位点的分析表明，在同源二聚体界面的环区域影响KS底物特异性。我们还描述了一个模型的催化结构域与酰基载体蛋白（ACP）结构域的相互作用。ACP被提议停靠在KS和AT结构域之间的深裂缝内，具有跨越KS同二聚体和AT结构域的相互作用。结合其他最近的数据，我们的研究结果提供了几个催化相关的蛋白质相互作用在这个显着的模块化megasynthases家族的原子分辨率的图片。
We report the 2.6 angstrom X-ray crystal structure of a 190 kDa homodimeric fragment from module 3 of the 6-deoxyerthronolide B synthase covalently bound to the inhibitor cerulenin. The structure shows two well-organized interclomain linker regions in addition to the full-length ketosynthase (KS) and acyltransferase (AT) domains. Analysis of the substrate-binding site of the KS domain suggests that a loop region at the homodimer interface influences KS substrate specificity. We also describe a model for the interaction of the catalytic domains with the acyl carrier protein (ACP) domain. The ACP is proposed to dock within a deep cleft between the KS and AT domains, with interactions that span both the KS homodimer and AT domain. In conjunction with other recent data, our results provide atomic resolution pictures of several catalytically relevant protein interactions in this remarkable family of modular megasynthases.