Structural insights into the catalytic and inhibitory mechanisms of the flavin transferase FmnB in Listeria monocytogenes.
Structural insights into the catalytic and inhibitory mechanisms of the flavin transferase FmnB in Listeria monocytogenes.
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单核细胞增生李斯特菌中黄素转移酶 FmnB 催化和抑制机制的结构见解
作者：
Zheng Y;Yan W;Dou C;Zhou D;Chen Y;Jin Y;Yang L;Zeng X;Cheng W
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. Flavin transferase FmnB is a key protein of the extracellular electron transfer pathway in Listeria monocytogenes, which can hydrolyze flavin adenine dinucleotide and transfer flavin mononucleotide. We analyzed the apo form of the enzyme and the complex structure of the binding substrate, as well as the complex structures of the binding three inhibitors, and identified key residues that affect enzyme activity.
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