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Nitrosoamphetamine binding to myoglobin and hemoglobin: Crystal structure of the H64A myoglobin-nitrosoamphetamine adduct.

ABSTRACT: N-hydroxyamphetamine (AmphNHOH) is an oxidative metabolite of amphetamine and methamphetamine. It is known to form inhibitory complexes upon binding to heme proteins. However, its interactions with myoglobin (Mb) and hemoglobin (Hb) have not been reported. We demonstrate that the reactions of AmphNHOH with ferric Mb and Hb generate the respective heme-nitrosoamphetamine derivatives characterized by UV-vis spectroscopy. We have determined the X-ray crystal structure of the H64A Mb-nitrosoamphetamine complex to 1.73 Å resolution. The structure reveals the N-binding of the nitroso-d-amphetamine isomer, with no significant H-bonding interactions between the ligand and the distal pocket amino acid residues.

SUBMITTER: Wang B

PROVIDER: S-EPMC5548592 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Nitrosoamphetamine binding to myoglobin and hemoglobin: Crystal structure of the H64A myoglobin-nitrosoamphetamine adduct.

Wang Bing B Powell Samantha M SM Guan Ye Y Xu Nan N Thomas Leonard M LM Richter-Addo George B GB

Nitric oxide : biology and chemistry 20170424

N-hydroxyamphetamine (AmphNHOH) is an oxidative metabolite of amphetamine and methamphetamine. It is known to form inhibitory complexes upon binding to heme proteins. However, its interactions with myoglobin (Mb) and hemoglobin (Hb) have not been reported. We demonstrate that the reactions of AmphNHOH with ferric Mb and Hb generate the respective heme-nitrosoamphetamine derivatives characterized by UV-vis spectroscopy. We have determined the X-ray crystal structure of the H64A Mb-nitrosoamphetam ...[more]

PMID: 28450187

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