通过联合量子力学/分子力学元动力学模拟研究的kinesin中的腺三酸盐水解机制
Matthew J McGrath1, I-F Will Kuo, Shigehiko Hayashi
1Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan. mcgrath@theory.biophys.kyoto-u.ac.jp
Journal of the American Chemical Society
|June 12, 2013
概括
基因素电机蛋白Eg5使用双水链机制进行ATP水解,由破碎的盐桥促进. 这一过程在ADP-bound国家不那么有利,这表明一个共同的动力机制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 计算化学计算化学
背景情况:
- 氨酸是分子电机,将从氨酸三酸盐 (ATP) 水解中的化学能量转化为机械工作.
- 虽然已知素的结构和运动性,但活性部位内的ATP水解的确切机制尚不清楚.
研究的目的:
- 为了阐明 ATP 水解机制在基因素-5 蛋白质 Eg5.5.
- 用计算模拟来确定ATP水解中涉及的关键步骤和中间体.
主要方法:
- 使用了量子力学/分子力学 (QM/MM) 组合的元动力学模拟.
- 在催化站点中计算了大约200个原子的自由能量表面.
主要成果:
- 确定了一条涉及两个水链的低屏障水解路径.
- 反应受益于Glu270和Arg234.4之间暂时断裂的盐桥.
- 由于固态阻碍和水分子相互作用,ATP水解在ADP结合的形状中不太有利.
结论:
- 识别的双水链机制为Eg5的ATP水解提供了洞察力.
- 这些发现表明,在不同的分子电机 (如肌和F1-ATPase) 上存在潜在的ATP水解机制.
相关概念视频
ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
Hydrolysis of ATP
The bonds of adenosine triphosphate (ATP) can be broken through the addition of water, releasing one or two phosphate groups in an exergonic process called hydrolysis. This reaction liberates the energy in the bonds for use in the cell—for instance, to synthesize proteins from amino acids.
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
Hydrolysis of ATP
The bonds of adenosine triphosphate (ATP) can be broken through the addition of water, releasing one or two phosphate groups in an exergonic process called hydrolysis. This reaction liberates the energy in the bonds for use in the cell—for instance, to synthesize proteins from amino acids.
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
ATP Driven Pumps I: An Overview
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
The Movement of Organelles and Vesicles
In eukaryotic cells, cytoskeletal filaments such as actin, microtubules, and intermediate filaments form a mesh-like cytoskeletal network. These filaments serve as tracks for transporting cellular cargo. Specialized motor proteins use the chemical energy stored in adenosine triphosphate (ATP) for this transport. During interphase, microtubules are polarized, with the plus-end towards the cell periphery and the minus-end towards the cell center. Two microtubule-associated motor proteins,...
ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...


