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HDX-MS of NicA2 and a NicA2 variant with increased activity

ABSTRACT: Here we have used HDX-MS to investigate the change in structure/dynamics in NicA2 and a variant with increased activity (v321) that was generated using directed evolution

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Antonio Calabrese

LAB HEAD: Antonio Calabrese

PROVIDER: PXD037151 | Pride | 2023-11-16

REPOSITORIES: Pride

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Directed evolution unlocks oxygen reactivity for a nicotine-degrading flavoenzyme.

Dulchavsky Mark M Mitra Rishav R Wu Kevin K Li Joshua J Boer Karli K Liu Xiaomeng X Zhang Zhiyao Z Vasquez Cristian C Clark Christopher T CT Funckes Kaitrin K Shankar Kokila K Bonnet-Zahedi Selene S Siddiq Mohammad M Sepulveda Yadira Y Suhandynata Raymond T RT Momper Jeremiah D JD Calabrese Antonio N AN George Olivier O Stull Frederick F Bardwell James C A JCA

Nature chemical biology 20230928 11

The flavoenzyme nicotine oxidoreductase (NicA2) is a promising injectable treatment to aid in the cessation of smoking, a behavior responsible for one in ten deaths worldwide. NicA2 acts by degrading nicotine in the bloodstream before it reaches the brain. Clinical use of NicA2 is limited by its poor catalytic activity in the absence of its natural electron acceptor CycN. Without CycN, NicA2 is instead oxidized slowly by dioxygen (O<sub>2</sub>), necessitating unfeasibly large doses in a therape ...[more]

PMID: 37770699

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