重新定义EryM乙转移酶在天然产品生物合成途径中的作用
bioRxiv : the preprint server for biology
|March 31, 2025
概括
埃里姆是一种与GCN5相关的N-乙转移酶 (GNAT),被认为是一种脱碳酶,但实际上只是一种乙转移酶. 结构和功能研究揭示了它在天然产品生物合成中的真正作用.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 酸超级家族具有多种不同的催化活动,包括乙转移和脱碳化.
- 来自Saccharopolyspora erythraea的EryM在历史上与乙转移酶和脱酶在红色素生物合成中的功能有关.
研究的目的:
- 阐明EryM所谓的双重催化活动的结构基础.
- 为了功能性地描述EryM,并澄清其在天然产品生物合成中的作用.
主要方法:
- 通过X射线晶体学,确定以自由形式和与乙-CoA复合的EryM的结构.
- 在体外功能测试以评估酶活性.
- 对EryM及其同类进行比较分析和生物信息分析.
主要成果:
- 晶体结构揭示了EryM的活跃站点架构和基板相互作用.
- 功能性测试证实,EryM可催化转移,但缺乏脱碳活化活性.
- 在N-转移的GNAT酶中发现了一个保存的催化口袋.
结论:
- EryM被重新定义为一种乙转移酶,挑战了关于其生物合成作用的先前假设.
- 这些发现为了解天然产品生物合成中GNAT酶的功能多样性提供了基础.
- 定义了一个广泛的GNAT子家族,涉及微生物通路.
相关概念视频
Phase II Reactions: Acetylation Reactions
145
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
145
Export of Misfolded Proteins out of the ER
3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K
Protein Modifications in the RER
4.9K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
4.9K
The Unfolded Protein Response
4.3K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.3K
Smooth Endoplasmic Reticulum
5.4K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
5.4K
tRNA Activation
18.7K
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
18.7K


