氨酸A. 氨酸A. 是一种氨酸. 一种天然存在的人类DNA的毒素topoisomerase I毒素
Ali Cagir1, Shannon H Jones, Rong Gao
1Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.
Journal of the American Chemical Society
|November 6, 2003
概括
来自Peganum nigellastrum的卢托宁A,稳定了人类DNA拓酶I,类似于坎普托塞辛. 这种机制解释了它的细胞毒性作用,并有助于设计新的癌症药物.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 自然产品 化学 化学
背景情况:
- 氨酸A是一种来自Peganum nigellastrum的pyrroloquinazolinoquinoline类化合物.
- 之前的研究表明它对小鼠白血病P-388细胞的细胞毒性.
- 卢托宁A的作用机制仍然没有被阐明.
研究的目的:
- 为了阐明卢托宁A的作用机制.
- 为了研究它与人类DNA拓聚酶I的相互作用.
- 为了比较它的活性与camptothecin.
主要方法:
- 人类DNA拓聚酶I-DNA共价二元复合物的稳定试验.
- 分析DNA裂变模式的分析.
- 在Saccharomyces cerevisiae中对托皮索马酶I依赖的细胞毒性测定.
主要成果:
- 发现卢托宁A可以稳定人体DNA拓酶I-DNA共价二元复合体.
- 它产生了一个类似于camptothecin的DNA裂变模式.
- 在表达人类毒酶I的酵母模型中,卢托宁A表现出托酶I依赖的细胞毒性.
结论:
- 卢托宁A通过稳定人体DNA拓酶I-DNA复合体而起作用.
- 这种机制与坎普托塞辛的机制相似.
- 这些发现提供了关于洛托尼A细胞毒性作用的见解,并为癌症治疗的新型坎普托西因类型的设计提供了信息.
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相关概念视频
Mutations
Overview
DNA Topoisomerases
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. Type I...
Types and Mechanism of action
Topoisomerases are divided into two main types. Type I...
Allosteric 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,...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Physical Properties of Amines
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
