当前位置：
X-MOL 学术
›
Biochemistry
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Recognition of DNA Supercoil Geometry by Mycobacterium tuberculosis Gyrase
Biochemistry ( IF 2.9 ) Pub Date : 2017-09-25 00:00:00 , DOI: 10.1021/acs.biochem.7b00681 Rachel E. Ashley , Tim R. Blower 1 , James M. Berger 1 , Neil Osheroff 2
Biochemistry ( IF 2.9 ) Pub Date : 2017-09-25 00:00:00 , DOI: 10.1021/acs.biochem.7b00681 Rachel E. Ashley , Tim R. Blower 1 , James M. Berger 1 , Neil Osheroff 2
Affiliation
|
Mycobacterium tuberculosis encodes only a single type II topoisomerase, gyrase. As a result, this enzyme likely carries out the cellular functions normally performed by canonical gyrase and topoisomerase IV, both in front of and behind the replication fork. In addition, it is the sole target for quinolone antibacterials in this species. Because quinolone-induced DNA strand breaks generated on positively supercoiled DNA ahead of replication forks and transcription complexes are most likely to result in permanent genomic damage, the actions of M. tuberculosis gyrase on positively supercoiled DNA were investigated. Results indicate that the enzyme acts rapidly on overwound DNA and removes positive supercoils much faster than it introduces negative supercoils into relaxed DNA. Canonical gyrase and topoisomerase IV distinguish supercoil handedness differently during the DNA cleavage reaction: while gyrase maintains lower levels of cleavage complexes on overwound DNA, topoisomerase IV maintains similar levels of cleavage complexes on both over- and underwound substrates. M. tuberculosis gyrase maintained lower levels of cleavage complexes on positively supercoiled DNA in the absence and presence of quinolone-based drugs. By retaining this important feature of canonical gyrase, the dual function M. tuberculosis type II enzyme remains a safe enzyme to act in front of replication forks and transcription complexes. Finally, the N-terminal gate region of the enzyme appears to be necessary to distinguish supercoil handedness during DNA cleavage, suggesting that the capture of the transport segment may influence how gyrase maintains cleavage complexes on substrates with different topological states.
中文翻译：
结核分枝杆菌回旋酶对DNA超螺旋几何的识别
结核分枝杆菌仅编码单一的II型拓扑异构酶，回旋酶。结果，该酶可能在复制叉的前面和后面执行通常由规范促旋酶和拓扑异构酶IV履行的细胞功能。此外，它是该物种中喹诺酮类抗菌剂的唯一目标。因为在复制叉和转录复合物之前，喹诺酮诱导的超螺旋DNA上产生的DNA链断裂最有可能导致永久性基因组损伤，所以结核分枝杆菌的作用研究了超螺旋阳性DNA上的Gyrase。结果表明，该酶可快速作用于覆盖的DNA，并能比将阴性超螺旋引入松弛的DNA更快地去除阳性超螺旋。典范的促旋酶和拓扑异构酶IV在DNA裂解反应过程中区分了超螺旋操纵性：虽然促旋酶在覆盖的DNA上保持较低的裂解复合物水平，但是拓扑异构酶IV在过交和欠绕的底物上均保持相似水平的裂解复合物。在不存在和存在喹诺酮类药物的情况下，结核分枝杆菌促旋酶在正超螺旋DNA上维持较低水平的裂解复合物。通过保留标准促旋酶的这一重要特征，双重功能的结核分枝杆菌II型酶仍然是在复制叉和转录复合物之前起作用的安全酶。最后，该酶的N末端门区域似乎是区分DNA切割过程中超螺旋反应性所必需的，这表明转运区段的捕获可能会影响回旋酶如何维持具有不同拓扑状态的底物上的切割复合物。
更新日期：2017-09-26
中文翻译：
结核分枝杆菌回旋酶对DNA超螺旋几何的识别
结核分枝杆菌仅编码单一的II型拓扑异构酶，回旋酶。结果，该酶可能在复制叉的前面和后面执行通常由规范促旋酶和拓扑异构酶IV履行的细胞功能。此外，它是该物种中喹诺酮类抗菌剂的唯一目标。因为在复制叉和转录复合物之前，喹诺酮诱导的超螺旋DNA上产生的DNA链断裂最有可能导致永久性基因组损伤，所以结核分枝杆菌的作用研究了超螺旋阳性DNA上的Gyrase。结果表明，该酶可快速作用于覆盖的DNA，并能比将阴性超螺旋引入松弛的DNA更快地去除阳性超螺旋。典范的促旋酶和拓扑异构酶IV在DNA裂解反应过程中区分了超螺旋操纵性：虽然促旋酶在覆盖的DNA上保持较低的裂解复合物水平，但是拓扑异构酶IV在过交和欠绕的底物上均保持相似水平的裂解复合物。在不存在和存在喹诺酮类药物的情况下，结核分枝杆菌促旋酶在正超螺旋DNA上维持较低水平的裂解复合物。通过保留标准促旋酶的这一重要特征，双重功能的结核分枝杆菌II型酶仍然是在复制叉和转录复合物之前起作用的安全酶。最后，该酶的N末端门区域似乎是区分DNA切割过程中超螺旋反应性所必需的，这表明转运区段的捕获可能会影响回旋酶如何维持具有不同拓扑状态的底物上的切割复合物。
京公网安备 11010802027423号