Ray Ashish Kumar, Bhowmik Somok, Saini Snehlata, Hussain Arsalan, Bakht Perwez, Pandey Shivam, Pathania Ranjana
Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, Uttarakhand, India.
Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, Uttarakhand, India; Centre of Excellence in Disaster Mitigation and Management, Indian Institute of Technology, Roorkee, Uttarakhand, India.
J Biol Chem. 2025 Aug 5;301(9):110549. doi: 10.1016/j.jbc.2025.110549.
Superoxide dismutase (SOD), a widely distributed metalloenzyme across all domains of life, mitigates the harmful effects of reactive oxygen species generated during oxidative stress. The catalytic activity of SOD depends on specific metal cofactor, which is determined by bioavailability, structural compatibility, and environmental factors. The nosocomial pathogen Acinetobacter baumannii has been able to thrive under oxidative stress with SODs imparting a major role in curbing this distress. However, the functional role of two encoded SODs, namely SodB and SodC in A. baumannii, is poorly understood in mitigating oxidative stress. Furthermore, the metal ion specificities of these SodB and SodC families exemplify a knowledge gap, as the metal ion utilized by individual family members cannot be reliably predicted. Our study unveils the specific metal cofactors utilized by SodB and SodC and their role in quenching host-mediated oxidative stress during infection by A. baumannii 5075 (AB5075), a hypervirulent and multidrug-resistant strain. The study reveals that SodB primarily utilizes Mn, whereas SodC employs Cu to achieve optimal catalytic efficiency in superoxide dismutation. The oxidative stress response in AB5075 favors SodB over SodC, highlighting the critical role of Mn-dependent SodB in counteracting oxidative stress. Furthermore, we demonstrated that mutations in metal-binding residues (SodB, SodB, SodC, and SodC) led to significant impairment of SOD activity, thus highlighting the importance of these residues in catalytic function and preference for metal ion cofactor. The study shows that SodB has identical metal ion-binding residues for both Fe and Mn but is only active with Mn ion.
超氧化物歧化酶（SOD）是一种广泛分布于生命所有领域的金属酶，可减轻氧化应激期间产生的活性氧的有害影响。SOD的催化活性取决于特定的金属辅因子，这由生物可利用性、结构兼容性和环境因素决定。医院病原体鲍曼不动杆菌能够在氧化应激下茁壮成长，其中SOD在缓解这种应激中起主要作用。然而，鲍曼不动杆菌中两个编码的SOD，即SodB和SodC在减轻氧化应激方面的功能作用尚不清楚。此外，这些SodB和SodC家族的金属离子特异性体现了知识空白，因为无法可靠预测单个家族成员所利用的金属离子。我们的研究揭示了SodB和SodC所利用的特定金属辅因子及其在高毒力和多重耐药菌株鲍曼不动杆菌5075（AB5075）感染期间淬灭宿主介导的氧化应激中的作用。该研究表明，SodB主要利用Mn，而SodC利用Cu以在超氧化物歧化中实现最佳催化效率。AB5075中的氧化应激反应对SodB的偏好高于SodC，突出了Mn依赖性SodB在抵抗氧化应激中的关键作用。此外，我们证明金属结合残基（SodB、SodB、SodC和SodC）中的突变导致SOD活性显著受损，从而突出了这些残基在催化功能和对金属离子辅因子偏好中的重要性。该研究表明，SodB对Fe和Mn具有相同的金属离子结合残基，但仅对Mn离子有活性。
