Human ARMT1 structure and substrate specificity indicates that it is a DUF89 family damage-control phosphatase.

Autor: Dennis TN; Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA., Kenjić N; Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA., Kang AS; Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA., Lowenson JD; Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA., Kirkwood JS; Metabolomics Core Facility, Institute for Integrative Genome Biology, University of California, Riverside, Riverside, CA 92521, USA., Clarke SG; Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA., Perry JJP; Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA; The School of Biotechnology, Amrita University, Kollam 690525 Kerala, India. Electronic address: jeff.perry@ucr.edu.
Jazyk: angličtina
Zdroj: Journal of structural biology [J Struct Biol] 2020 Oct 01; Vol. 212 (1), pp. 107576. Date of Electronic Publication: 2020 Jul 15.
DOI: 10.1016/j.jsb.2020.107576
Abstrakt: Metabolite damage control is a critical but poorly defined aspect of cellular biochemistry, which likely involves many of the so far functionally uncharacterized protein domain (domains of unknown function; DUFs). We have determined the crystal structure of the human DUF89 protein product of the C6ORF211 gene to 1.85 Å. The crystal structure shows that the protein contains a core α-β-α fold with an active site-bound metal ion and α-helical bundle N-terminal cap, which are both conserved features of subfamily III DUF89 domains. The biochemical activities of the human protein are conserved with those of a previously characterized budding yeast homolog, where an in vitro phosphatase activity is supported by divalent cations that include Co 2+ , Ni 2+ , Mn 2+ or Mg 2+ . Full steady-state kinetics parameters of human DUF89 using a standard PNPP phosphatase assay revealed a six times higher catalytic efficiency in presence of Co 2+ compared to Mg 2+ . The human enzyme targets a number of phosphate substrates similar to the budding yeast homolog, while it lacks a previously indicated methyltransferase activity. The highest activity on substrate was observed with fructose-1-phosphate, a potent glycating agent, and thus human DUF89 phosphatase activity may also play a role in limiting the buildup of phospho-glycan species and their related damaged metabolites.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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