DOMAIN CLOSURE IN ADENYLATE KINASE - JOINTS ON EITHER SIDE OF 2 HELICES CLOSE LIKE NEIGHBORING FINGERS
DOMAIN CLOSURE IN ADENYLATE KINASE - JOINTS ON EITHER SIDE OF 2 HELICES CLOSE LIKE NEIGHBORING FINGERS
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DOI：
10.1006/jmbi.1993.1048
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发表时间：
1993-01-20
影响因子：
5.6
通讯作者：
CHOTHIA, C
中科院分区：
文献类型：
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作者：
GERSTEIN, M;SCHULZ, G;CHOTHIA, C
在腺苷酸激酶的大变体中，AMP和ATP底物被旋转90°的结构域掩埋。在这里负责这个域关闭的构象变化，确定通过分析牛心脏线粒体腺苷酸激酶的开放状态和关闭状态ofEscherichia coli腺苷酸激酶。虽然这两种蛋白质有序列差异，但导致结构域移动的主要结构变化很大，并且可以清楚地与进化的影响区分开来。移动的结构域通过两个以反平行方式堆积在一起的螺旋与蛋白质的其余部分连接。在闭合过程中，变形发生在四个局部区域，称为关节，这些螺旋的N和C端附近。这些关节中的三个关节具有简单的运动，可以通过三个扭转角的旋转来很好地近似，但是与配体接触的关节涉及整个延伸环的运动：即反向转弯两侧的两个扭转显著变化。接头的主链原子几乎没有堆积限制。第一对关节负责总旋转的0.30 °，第二对关节负责剩余的0.60 °。这些运动将关节、两个螺旋和移动的域的其余部分之间的区域沿着带到第一近似，作为刚体。这种联合域关闭机制与其他酶中发现的剪切机制形成对比。
In large variants of adenylate kinase the AMP and ATP substrates are buried by a domain rotating by 90°. Here conformational changes responsible for this domain closure are determined by an analysis of the open state of beef heart mitochondrial adenylate kinase and the closed state ofEscherichia coliadenylate kinase. Although these two proteins have sequence differences, the principal structural changes responsible for the domain movements are large, and can clearly be distinguished from the effects of evolution.The mobile domain is linked to the rest of the protein by two helices packed together in an antiparallel fashion. During the closure, deformations take place in four localized regions, called joints, near the N and C termini of these helices. Three of these joints have simple motions that can be well approximated by rotations of three torsion angles, but the joint that makes contact with the ligand involves motion throughout an extended loop: i.e. two torsions on either side of a reverse turn change significantly. The main chain atoms of the joints have few packing constraints. The first pair of joints is responsible for ∼30° of the total rotation and the second pair for the remaining ∼60°. These movements carries along the regions between the joints, the two helices and the rest of the mobile domain, to a first approximation, as rigid bodies. This jointed domain closure mechanism is contrasted with the shear mechanisms found in other enzymes.