耶尔西尼亚YopJ通过阻断酸化来乙化并抑制激酶激活
Sohini Mukherjee1, Gladys Keitany, Yan Li
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|May 27, 2006
概括
耶尔西尼亚尼亚是什么意思
科学领域:
- 微生物学和分子生物学
- 细胞信号传导和免疫学
背景情况:
- 耶尔西尼亚物种使用III型效应蛋白来破坏宿主真核细胞的信号通路.
- 关键的先天免疫路径,包括基激活蛋白激酶 (MAPK) 和核因子kappaB (NFkappaB),是Yersinia效应物的目标.
- 耶尔西尼亚效应剂YopJ通过阻断MAPK激酶 (MAPKKs) 的激活来特别抑制MAPK和NFkappaB信号传递.
研究的目的:
- 阐明Yersinia效应物YopJ抑制MAPKK激活的分子机制.
- 调查YopJ的酶活性及其在修改MAPKK蛋白质中的作用.
- 了解YopJ介导的修饰如何影响MAPKKs的酸化和激活.
主要方法:
- 生物化学测试以确定YopJ的酶活性.
- 使用YopJ和乙辅酶A (CoA) 进行MAPKK6的体外修饰.
- 在MAPKK6激活循环中对氨酸和氨酸残留物修饰的分析.
- 评估YopJ修改对MAPKK6酸化和激活的影响.
主要成果:
- YopJ作为一种乙转移酶,利用乙-CoA.
- 在MAPKK6.6的激活循环中,YopJ在MAPKK6.6的激活循环中对关键的氨酸和氨酸残留物进行乙化.
- 由YopJ进行的乙化直接与MAPKK6的酸化竞争并阻止其酸化,从而抑制其激活.
结论:
- 耶尔西尼亚的YopJ效应器通过乙化和阻断MAPKK激活来抑制宿主天生的免疫信号.
- 这种乙化机制作为酸化的直接竞争性抑制,防止下游信号.
- 通过乙化进行共价变异代表了生物信号通路中的潜在的一般调节机制.
相关概念视频
01:30Enzyme Inhibition
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
02:34Enzymes
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...