在 pyrrolnitrin 生物合成酶 PrnB 中阐明配体相互作用和小分子激活
Bingnan Li1, Remigio Usai1, Jackson Campbell1
1Department of Chemistry, University of Georgia, Athens, Georgia, USA.
The Journal of biological chemistry
|December 26, 2024
概括
罗利尼特林生物合成酶PrnB通过血协调结合基质,抑制一些反应,但激活其他反应. 这种酶表现出独特的催化机制,与其他氧化酶不同.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 抗真菌化合物生物合成
背景情况:
- 罗利尼特林是一种由 Pseudomonas 生产的强效抗真菌药物.
- 它的生物合成涉及四种酶,特别是 PrnB,一种血红酶.
- 由于体外活性挑战,PrnB的功能和催化机制仍然不太清楚.
研究的目的:
- 研究 PrnB 与基质和小分子的相互作用.
- 阐明基质结合和血红素激活的机制.
- 确定 PrnB 是否遵循已知的血红酶催化途径.
主要方法:
- 频谱技术 (UV-Vis,停止流动) 的使用
- 在X射线晶体学.
- 生物物理和生物化学测定.
主要成果:
- 基质氨基组与PrnB的血基直接协调.
- 这种协调可以抑制H2O2和CN-但不能抑制NO或O2的激活.
- 基于血红素的氧化剂形成,但缺乏催化活性,表明PrnB的独特机制.
结论:
- PrnB采用独特的催化机制,与其他依赖血红素的芳香氧酶不同.
- 在PrnB中结合联体和小分子激活在血红蛋白催化中呈现出一种新的范式.
- 这项研究为PrnB独特的功能提供了关键的见解.
相关概念视频
Ligand Binding Sites
12.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.7K
Allosteric Proteins-ATCase
5.7K
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...
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...
5.7K
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Biosynthesis of Nucleic Acids
2
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
2
Covalently Linked Protein Regulators
6.8K
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....
6.8K


