A human protein hydroxylase that accepts D-residues.

Autor: Choi H; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK.; Department of Bioscience and Biotechnology, Sejong University, 209 Neungdong-ro, Kwangjin-gu, Seoul, 05006, Korea., Hardy AP; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Leissing TM; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Chowdhury R; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Nakashima Y; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Ge W; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Markoulides M; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Scotti JS; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Gerken PA; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Thorbjornsrud H; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Kang D; Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Korea.; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea., Hong S; Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Korea.; Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea., Lee J; Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA., McDonough MA; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK., Park H; Department of Bioscience and Biotechnology, Sejong University, 209 Neungdong-ro, Kwangjin-gu, Seoul, 05006, Korea. hspark@sejong.ac.kr., Schofield CJ; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12, Mansfield Road, Oxford, OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk.
Jazyk: angličtina
Zdroj: Communications chemistry [Commun Chem] 2020 May 01; Vol. 3 (1), pp. 52. Date of Electronic Publication: 2020 May 01.
DOI: 10.1038/s42004-020-0290-5
Abstrakt: Factor inhibiting hypoxia-inducible factor (FIH) is a 2-oxoglutarate-dependent protein hydroxylase that catalyses C3 hydroxylations of protein residues. We report FIH can accept (D)- and (L)-residues for hydroxylation. The substrate selectivity of FIH differs for (D) and (L) epimers, e.g., (D)- but not (L)-allylglycine, and conversely (L)- but not (D)-aspartate, undergo monohydroxylation, in the tested sequence context. The (L)-Leu-containing substrate undergoes FIH-catalysed monohydroxylation, whereas (D)-Leu unexpectedly undergoes dihydroxylation. Crystallographic, mass spectrometric, and DFT studies provide insights into the selectivity of FIH towards (L)- and (D)-residues. The results of this work expand the potential range of known substrates hydroxylated by isolated FIH and imply that it will be possible to generate FIH variants with altered selectivities.
(© 2020. The Author(s).)
Databáze: MEDLINE
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