Structural insights into the catalytic and inhibitory mechanisms of the flavin transferase FmnB in Listeria monocytogenes
Yanhui Zheng,
Weizhu Yan,
Chao Dou,
Dan Zhou,
Yunying Chen,
Ying Jin,
Lulu Yang,
Xiaotao Zeng,
Wei Cheng
Affiliations
Yanhui Zheng
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Weizhu Yan
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Chao Dou
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Dan Zhou
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Yunying Chen
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Ying Jin
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Lulu Yang
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Xiaotao Zeng
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Wei Cheng
Division of Respiratory and Critical Care Medicine Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease‐Related Molecular Network State Key Laboratory of Biotherapy West China Hospital of Sichuan University Chengdu China
Abstract Listeria monocytogenes, a food‐borne Gram‐positive pathogen, often causes diseases such as gastroenteritis, bacterial sepsis, and meningitis. Newly discovered extracellular electron transfer (EET) from L. monocytogenes plays critical roles in the generation of redox molecules as electron carriers in bacteria. A Mg2+‐dependent protein flavin mononucleotide (FMN) transferase (FmnB; UniProt: LMRG_02181) in EET is responsible for the transfer of electrons from intracellular to extracellular by hydrolyzing cofactor flavin adenine dinucleotide (FAD) and transferring FMN. FmnB homologs have been investigated in Gram‐negative bacteria but have been less well studied in Gram‐positive bacteria. In particular, the catalytic and inhibitory mechanisms of FmnB homologs remain elusive. Here, we report a series of crystal structures of apo‐FmnB and FmnB complexed with substrate FAD, three inhibitors AMP, ADP, and ATP, revealing the unusual catalytic triad center (Asp301‐Ser257‐His273) of FmnB. The three inhibitors indeed inhibited the activity of FmnB in varying degrees by occupying the binding site of the FAD substrate. The key residue Arg262 of FmnB was profoundly affected by ADP but not AMP or ATP. Overall, our studies not only provide insights into the promiscuous ligand recognition behavior of FmnB but also shed light on its catalytic and inhibitory mechanisms.
