基因编码硫酸-l-氨酸与氨酸,氨酸和氨酸通过SuFEx在活体蛋白质中发生反应
Nanxi Wang1, Bing Yang1, Caiyun Fu1,2
1Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute , University of California San Francisco , 555 Mission Bay Boulevard South , San Francisco , California 94158 , United States.
Journal of the American Chemical Society
|March 31, 2018
概括
研究人员通过基因编码硫酸-l-氨酸 (FSY),一种新的非自然氨基酸,用于体内蛋白质的修饰. 这种生物相容的氨基酸可以通过硫交换 (SuFEx) 进行新的共价蛋白质工程.
科学领域:
- 生物化学
- 化学生物学
- 合成生物学
背景情况:
- 在体内引入蛋白质的新化学反应性使得先进的研究和工程应用成为可能.
- 潜在的生物反应性非自然氨基酸 (UAAS) 促进与自然氨基酸残留物之间的近距离共价键.
- 在体内应用中扩大UAAS的范围需要与多种自然残留物具有生物相容性.
研究的目的:
- 用硫交换 (SuFEx) 来进行体内蛋白质修饰的第一个潜伏生物反应性UAA.
- 评估FSY在活细胞中的生物相容性和反应性.
- 证明FSY在形成共价蛋白内桥梁和蛋白间交叉连接方面的有用性.
主要方法:
- 在大肠杆菌和哺乳动物细胞中硫酸-l-素 (FSY) 的遗传编码.
- 将FSY纳入目标蛋白质
- 在生理条件下通过硫交换 (SuFEx) 分析FSY与近位 lysine,histidine 和 tyrosine 的反应性.
主要成果:
- 在细菌和哺乳动物细胞中,FSY成功且无毒地被纳入蛋白质.
- 通过SuFEx,FSY选择性地与近位素,胺和氨酸残留物发生反应.
- 在活细胞内直接形成共价蛋白内桥梁和蛋白间交叉链接.
结论:
- 基因编码的FSY是一种生物相容和多功能Uaa用于体内蛋白质的操纵.
- 通过使用SuFEx点击化学,FSY可以实现近距离激活的多目标共价修饰.
- FSY为化学生物学,药物发现和生物治疗提供了一个强大的新工具.
相关概念视频
01:26Receptor Tyrosine Kinases
19.0K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
19.0K
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
561
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
561
02:04Covalently Linked Protein Regulators
9.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.7K
02:26Conservation of Protein Domains Over Different Proteins
14.7K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.7K
01:19Encoding
875
Information enters the brain through encoding, which is the input of information into the memory system. Once sensory information is received from the environment, the brain labels or codes it. The information is then organized with similar information and connected to existing concepts. Encoding occurs through automatic processing and effortful processing.
Automatic processing involves the encoding of details like time, space, frequency, and the meaning of words, usually done without conscious...
Automatic processing involves the encoding of details like time, space, frequency, and the meaning of words, usually done without conscious...
875
02:59Animal Mitochondrial Genetics
9.3K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
9.3K