Sugandhi Sapna, Rajmane Vyankatesh, Taunk Khushman, Jadhav Sushama, Nema Vijay, Rapole Srikanth, Mande Shekhar C
National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India.
Division of Molecular Biology, ICMR-National AIDS Research Institute, Pune, India.
Biochem Biophys Rep. 2023 Jul 14;35:101512. doi: 10.1016/j.bbrep.2023.101512. eCollection 2023 Sep.
encounters diverse microenvironments, including oxidative assault (ROS and RNS), when it attempts to establish itself within its human host. Therefore, redox sensory and regulation processes are assumed significant importance, as these are essential processes for to survive under these hostile conditions. contains thioredoxin system to maintain redox homeostasis, which establish a balance between the thiol/dithiol couple. Still very less is known about it. In the present study, we attempted to capture the targets of all the thioredoxin proteins (., TrxB and TrxC) and a thioredoxin-like protein, NrdH, under aerobic and hypoxic conditions by performing thioredoxin trapping chromatography followed by mass spectrometry. We found that TrxC captured the maximum number of targets in both the physiological conditions and most of the targets of TrxB and NrdH showing overlap with targets of TrxC, indicating that TrxC acts as main thioredoxin. Further the PANTHER classification system provides involvement of targets in various metabolic processes and Gene Ontology analysis suggests that glutamine biosynthetic process and Fe-S cluster biosynthesis are the most enriched processes in the target list of TrxC and TrxB respectively. Also, we suggest that the thioredoxin system might play an important role under hypoxia by targeting those proteins which are responsible to sense and maintain hypoxic conditions. Furthermore, our studies establish a link between TrxB and iron-sulfur cluster biogenesis in . Ultimately, these findings open a new direction to target the thioredoxin system for screening new anti-mycobacterial drug targets.
当它试图在人类宿主体内定植时，会遇到多种微环境，包括氧化攻击（活性氧和活性氮）。因此，氧化还原感应和调节过程被认为具有重要意义，因为这些是在这些恶劣条件下生存的基本过程。[具体生物名称]含有硫氧还蛋白系统以维持氧化还原稳态，该系统在硫醇/二硫醇对之间建立平衡。对此仍知之甚少。在本研究中，我们通过进行硫氧还蛋白捕获色谱法并结合质谱分析，试图捕获在需氧和缺氧条件下所有硫氧还蛋白（如TrxB和TrxC）以及一种硫氧还蛋白样蛋白NrdH的靶标。我们发现，在两种生理条件下，TrxC捕获的靶标数量最多，TrxB和NrdH的大多数靶标与TrxC的靶标重叠，这表明TrxC是主要的硫氧还蛋白。此外，PANTHER分类系统显示靶标参与各种代谢过程，基因本体分析表明谷氨酰胺生物合成过程和铁硫簇生物合成分别是TrxC和TrxB靶标列表中最丰富的过程。而且，我们认为硫氧还蛋白系统可能通过靶向那些负责感知和维持缺氧条件的蛋白质，在缺氧情况下发挥重要作用。此外，我们的研究在[具体生物名称]中建立了TrxB与铁硫簇生物合成之间的联系。最终，这些发现为靶向硫氧还蛋白系统以筛选新的抗分枝杆菌药物靶标开辟了新方向。
