来自Burkholderia thailandensis和Mycobacterium paratuberculosis的IspD的晶体结构和生物物理特征
Phillip G Pierce1, Brian E Hartnett2, Tosha M Laughlin2
1Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA.
Acta crystallographica. Section F, Structural biology communications
|February 2, 2024
概括
甲基酸 (MEP) 路径的甲基酸 (MEP) 路径.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- 甲基氨酸酸盐 (MEP) 途径对于细菌中的异烯酸生物合成至关重要.
- 由于它们在哺乳动物中不存在,MEP通路酶是抗感染药物发现的有吸引力的目标.
- IspD是MEP途径中的第三种酶.
研究的目的:
- 为了确定Burkholderia thailandensis IspD (BtIspD) 在apo和cytidine triphosphate (CTP) 结合状态中的晶体结构.
- 为了描述Mycobacterium paratuberculosis IspD (MpIspD) 的apo结构.
- 提供结构和生物物理数据,以促进IspD抑制剂的发现.
主要方法:
- 进行X射线晶体学以获得Apo和CTP结合的BtIspD结构,以及Apo的MpIspD结构.
- 循环二元化以评估MpIspD和BtIspD的化温度 (Tm).
- 异热定位热度计,以评估CTP对BtIspD的结合亲和力.
主要成果:
- 观察到CTP结合稳定了BtIspD.中的特定循环 (残留13-19).
- 对于MpIspD和BtIspD的中等Tm值表明热转移测试的可行性.
- 量化了CTP-CTP-BtIspD相互作用的结合 afinity 数据.
结论:
- 对CTP绑定的BtIspD的结构洞察力为合理的药物设计提供了基础.
- 生物物理特性支持使用热转移试验进行抑制剂选的潜力.
- 获得的数据对于开发针对MEP途径的新型抗感染药物非常有价值.
关键词:
这种植物是Burkholderia thailandensis.这是pDD的意思.这是一种Mycobacterium paratuberculosis的细菌.这是SSGCID的SSGCID.西雅图结构基因组学传染病中心.通过cytidylyl转移酶.结构基因组学是结构基因组学.转移酶是一种转移酶.更多相关视频
相关概念视频
Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Cytoskeletal Proteins in Bacteria
Bacterial cells were initially considered simple, randomly organized structures lacking a cytoskeleton. However, the discovery of cytoskeleton homologs in bacteria led to the change of this opinion. Bacterial cytoskeletal filaments regulate the cell shape, cell polarity, cell division, and partitioning of plasmids during cell division. It was later discovered that bacterial cytoskeletal proteins, mainly actin and tubulin homologs, are diverse compared to their eukaryotic counterparts. On the...
Endospores and Sporulation
Endospores are specialized, dormant cells primarily formed by Gram-positive bacteria, including Bacillus and Clostridium, enabling survival under extreme environmental conditions. Due to their unique composition and formation process, these structures are highly resistant to physical and chemical insults, such as extreme heat, ultraviolet and ionizing radiation, desiccation, and toxic chemicals. Rare instances of endospore-like structures have also been observed in some Gram-negative bacteria,...
Bacterial Phylum Actinobacteria
Coryneform bacteria are gram-positive, aerobic, nonmotile rods that exhibit irregular, club-shaped, or V-shaped arrangements. Their V-shape results from snapping division, where the inner cell wall layer forms the cross-wall, while the outer layer remains intact until it ruptures on one side, causing the daughter cells to bend away.The primary genera are Corynebacterium and Arthrobacter. Corynebacterium includes diverse species, ranging from saprophytes to pathogens like Corynebacterium...
DNA Bacteriophages
Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
Tuberculosis
Tuberculosis (TB) remains a significant global health concern, primarily targeting the lungs and spreading through airborne transmission. Infection begins when aerosolized droplet nuclei, expelled by an individual with active TB, are inhaled by another person. These microscopic particles carry Mycobacterium tuberculosis, the causative agent of TB. Upon reaching the alveoli, the bacilli are engulfed by alveolar macrophages. However, due to their specialized lipid-rich cell wall, these pathogens...


