抑 HIF 因子能催化锚蛋白折叠蛋白 VNVN 基序中两个天冬酰胺残基的羟化反应。
Factor inhibiting HIF can catalyze two asparaginyl hydroxylations in VNVN motifs of ankyrin fold proteins.
机构信息
Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, United Kingdom; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, United Kingdom.
出版信息
J Biol Chem. 2022 Jun;298(6):102020. doi: 10.1016/j.jbc.2022.102020. Epub 2022 May 7.
The aspariginyl hydroxylase human factor inhibiting hypoxia-inducible factor (FIH) is an important regulator of the transcriptional activity of hypoxia-inducible factor. FIH also catalyzes the hydroxylation of asparaginyl and other residues in ankyrin repeat domain-containing proteins, including apoptosis stimulating of p53 protein (ASPP) family members. ASPP2 is reported to undergo a single FIH-catalyzed hydroxylation at Asn-986. We report biochemical and crystallographic evidence showing that FIH catalyzes the unprecedented post-translational hydroxylation of both asparaginyl residues in "VNVN" and related motifs of ankyrin repeat domains in ASPPs (i.e., ASPP1, ASPP2, and iASPP) and the related ASB11 and p18-INK4C proteins. Our biochemical results extend the substrate scope of FIH catalysis and may have implications for its biological roles, including in the hypoxic response and ASPP family function.
asparaginyl 羟化酶人因子抑制缺氧诱导因子 (FIH) 是缺氧诱导因子转录活性的重要调节剂。FIH 还催化锚蛋白重复结构域蛋白中 asparaginyl 和其他残基的羟化，包括凋亡刺激 p53 蛋白 (ASPP) 家族成员。据报道，ASPP2 经历了 FIH 催化的单一 asparaginyl 残基的羟化，位于 Asn-986。我们报告了生化和晶体学证据，表明 FIH 催化了 ASPPs（即 ASPP1、ASPP2 和 iASPP）和相关的 ASB11 和 p18-INK4C 蛋白中“VNVN”和相关锚蛋白重复结构域基序中 asparaginyl 残基的前所未有的翻译后羟化。我们的生化结果扩展了 FIH 催化的底物范围，可能对其生物学作用具有意义，包括在低氧反应和 ASPP 家族功能中。
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