在ATP结合蛋白中,正电荷残留物与腺因的多种分子间相互作用模式与ATP结合蛋白
Lisong Mao1, Yanli Wang, Yuemin Liu
1Department of Chemistry, University of Toledo, Toledo, OH 43606, USA.
Journal of the American Chemical Society
|November 20, 2003
概括
研究人员通过分析氨酸和氨酸等带电残留物,发现了蛋白质如何识别氨酸5'-三酸盐 (ATP). 这一发现对于理解酶机制和开发新药至关重要.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算化学计算化学
背景情况:
- 氨酸5-三酸盐 (ATP) 对所有生命形式至关重要.
- 了解蛋白质对ATP的识别是酶研究和药物发现的关键.
研究的目的:
- 分析ATP结合蛋白中腺基识别的分子决定因素.
- 为了识别带电残留物与腺因基相互作用的新型模式.
主要方法:
- 蛋白质数据库 (PDB) 的大规模数据挖掘.
- 对充电残留物在腺因基周围分布的分析.
- 使用MP2级和SM5.42R溶解模型对分子间相互作用能量的计算分析.
主要成果:
- 确定了充电残留物的新型分布模式:在氨酸的N7侧附近的氨酸残留物,在氨酸上方或下方的氨酸残留物.
- 氨酸-氨酸相互作用涉及阴离子-π和键.
- 氨酸-氨酸相互作用涉及阴离子-pi和pi-pi堆叠.
- 为这些代表性相互作用计算了显著的相互作用强度.
结论:
- 已确定的带电残留模式促进了与腺因基的多重,强烈的分子间相互作用.
- 这种对ATP-蛋白相互作用的详细理解可以为设计针对ATP结合蛋白的新疗法提供信息.
相关概念视频
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 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...
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...
The ADP/ATP Carrier Protein
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
ATP Energy Storage and Release
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP and inorganic phosphate (Pi), and the free energy released during this process is lost as heat. The energy released by ATP hydrolysis is used to perform work inside the cell and depends on a strategy called energy coupling. Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed.
One example of energy coupling using ATP involves a...
One example of energy coupling using ATP involves a...
ATP Energy Storage and Release
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP and inorganic phosphate (Pi), and the free energy released during this process is lost as heat. The energy released by ATP hydrolysis is used to perform work inside the cell and depends on a strategy called energy coupling. Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed.
One example of energy coupling using ATP involves a...
One example of energy coupling using ATP involves a...


