TY - JOUR
T1 - A human protein hydroxylase that accepts D-residues
AU - Choi, Hwanho
AU - Hardy, Adam P.
AU - Leissing, Thomas M.
AU - Chowdhury, Rasheduzzaman
AU - Nakashima, Yu
AU - Ge, Wei
AU - Markoulides, Marios
AU - Scotti, John S.
AU - Gerken, Philip A.
AU - Thorbjornsrud, Helen
AU - Kang, Dahye
AU - Hong, Sungwoo
AU - Lee, Joongoo
AU - McDonough, Michael A.
AU - Park, Hwangseo
AU - Schofield, Christopher J.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85084154662&partnerID=8YFLogxK
U2 - 10.1038/s42004-020-0290-5
DO - 10.1038/s42004-020-0290-5
M3 - 学術論文
AN - SCOPUS:85084154662
SN - 2399-3669
VL - 3
JO - Communications Chemistry
JF - Communications Chemistry
IS - 1
M1 - 52
ER -