What is the relationship between the global structures of apo and holo proteins?
What is the relationship between the global structures of apo and holo proteins?
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DOI：
10.1002/prot.21510
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发表时间：
2008-02-01
影响因子：
2.9
通讯作者：
Skolnick, Jeffrey
中科院分区：
文献类型：
--
作者：
Brylinski, Michal;Skolnick, Jeffrey
众所周知，配体结合和释放可诱导受体蛋白的广泛结构变化，从结合口袋中的环或侧链的小运动到大规模结构域铰链弯曲抗剪切运动或甚至促进配体捕获和释放的部分解折叠。一个有趣的问题是，一般来说，配体结合引发的构象变化是什么？这项工作的目的是分析蛋白质中的结构变化的幅度导致配体结合，以评估是否配体结合的状态需要包括在基于模板的蛋白质结构预测算法。为了解决这个问题，创建了无配体和配体结合形式的521对蛋白质结构的非冗余数据集，并用于估计apo和holo形式之间的局部和全局结构相似性程度。在大多数情况下，蛋白质在配体结合/释放时经历其三级结构的相对小的构象重排（与天然RMSA的大多数均方根偏差为
It is well known that ligand binding and release may induce a wide range of structural changes in a receptor protein, varying from small movements of loops or side chains in the binding pocket to large-scale domain hinge-bending anti shear motions or even partial unfolding that facilitates the capture and release of a ligand. An interesting question is what in general are the conformational changes triggered by ligand binding? The aim of this work is analyze the magnitude of structural changes in a protein resulting from ligand binding to assess if the state of ligand binding needs to be included in template-based protein structure prediction algorithms. To address this issue, a nonredundant dataset of 521 paired protein structures in the ligand-free and ligand-bound form was created and used to estimate the degree of both local and global structure similarity between the apo and holo forms. In most cases, the proteins undergo relatively small conformational rearrangements of their tertiary structure upon ligand binding/release (most root-mean-square-deviations from native, RMSA are