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Purification, Crystallization, and Preliminary Crystallographic Studies of Human As(III) S-Adenosylmethionine Methyltransferase (hAS3MT)

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Abstract

Exposure to environmental arsenic is associated with serious of health issues such as cancer, diabetes and developmental delays in infants and children. In human liver, As(III) S-adenosylmethionine methyl transferase (hAS3MT) (EC 2.1.1.137) was proposed to be an detoxification process by methylation of inorganic arsenite into pentavalent methyl MAs(V) and dimethyl arsenite DMAs(V). More recently the first product was shown to be highly toxic and potentially carcinogenic trivalent methylarsenite (MAs(III)). Our studies are designed to elucidate the mechanism of AS3MT and its contribution to arsenic-related diseases. Here, we report the first crystallization and preliminary X-ray diffraction analysis of the human AS3MT enzyme. The crystals belong to the monoclinic P1211 space group with unit cell parameters of a = 135.03 Å, b = 260.44 Å, c = 279.03 Å, α = 90.00°, β = 93.36°, γ = 90.00°.

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ACKNOWLEDGMENTS

This project was supported by NIH grants ES023779, GM55425, and GM136211 to bpr. The project utilized the Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory. SER-CAT is supported by its member institutions (see www.ser-cat.org/members.html), and equipment grants (S10_RR25528 and S10_RR028976) from the National Institutes of Health. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. We also acknowledge the Berkeley Center for Structural Biology, Lawrence Berkeley Laboratory, CA, USA for data collection. The Berkeley Center for Structural Biology is supported in part by Howard Hughes Medical Institute and The ALS-ENABLE beamlines are supported in part by the National Institutes of Health, National Institute of General Medical Sciences, grant P30 GM124169.

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Authors and Affiliations

  1. Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, FL.33199, Miami, USA

    M. Radhakrishnan, C. Packianathan & B. P. Rosen

  2. Department of Chemistry, Texas A&M University, College Station, Texas, TX, USA

    C. Packianathan

  3. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley Laboratory, BLDG 6R2100, CA 94720, Berkeley, USA

    B. Sankaran

  4. SER-CAT and the Department of Biochemistry and Molecular Biology, University of Georgia, GA 30602, Athens, USA

    P. Kandavelu

Authors
  1. M. Radhakrishnan
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  2. C. Packianathan
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  3. B. Sankaran
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  4. P. Kandavelu
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  5. B. P. Rosen
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Contributions

All authors contributed to the study conception and design. Material preparation, experimental design and data analysis were performed by Manohar Radhakrishnan and Charles Packianathan. Data collection at synchrotrons was performed by Banumathi Sankaran and Palani Kandavelu. The overall design of the project was the concept of Barry P. Rosen. The first drafts of the manuscript were written by Manohar Radhakrishnan and Barry P. Rosen, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to B. P. Rosen.

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Radhakrishnan, M., Packianathan, C., Sankaran, B. et al. Purification, Crystallization, and Preliminary Crystallographic Studies of Human As(III) S-Adenosylmethionine Methyltransferase (hAS3MT). Crystallogr. Rep. 66, 1311–1315 (2021). https://doi.org/10.1134/S1063774521070129

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  • DOI: https://doi.org/10.1134/S1063774521070129

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