Journal ArticleDOI
FeII/alpha-ketoglutarate-dependent hydroxylases and related enzymes.
Reads0
Chats0
TLDR
The reactions catalyzed by this superfamily of enzymes are described, key active site features revealed by structural studies are highlighted, and results from spectroscopic and other approaches that provide insights into the chemical mechanisms are summarized.Citations
More filters
Journal ArticleDOI
The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate–Dependent Nucleic Acid Demethylase
Thomas Gerken,Christophe Girard,Yi-Chun Loraine Tung,Celia J. Webby,Vladimir Saudek,Kirsty S. Hewitson,Giles S.H. Yeo,Michael A. McDonough,Sharon Cunliffe,Luke A. McNeill,Juris Galvanovskis,Patrik Rorsman,Peter Robins,Xavier Prieur,Anthony P. Coll,Marcella Ma,Zorica Jovanovic,I. Sadaf Farooqi,Barbara Sedgwick,Inês Barroso,Tomas Lindahl,Chris P. Ponting,Frances M. Ashcroft,Stephen O'Rahilly,Christopher J. Schofield +24 more
TL;DR: It is found that recombinant murine Fto catalyzes the Fe(II)- and 2OG-dependent demethylation of 3-methylthymine in single-stranded DNA, with concomitant production of succinate, formaldehyde, and carbon dioxide.
Journal ArticleDOI
Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine
Chun-Xiao Song,Keith E. Szulwach,Ye Fu,Qing Dai,Chengqi Yi,Xuekun Li,Yujing Li,Chih Hsin Chen,Wen Zhang,Xing Jian,Jing Wang,Li Zhang,Timothy J. Looney,Baichen Zhang,Lucy A. Godley,Leslie M. Hicks,Bruce T. Lahn,Peng Jin,Chuan He +18 more
TL;DR: This method uses the T4 bacteriophage β-glucosyltransferase to transfer an engineered glucose moiety containing an azide group onto the hydroxyl group of 5-hmC, a recently identified epigenetic modification present in substantial amounts in certain mammalian cell types.
Journal ArticleDOI
Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors
Mengtao Xiao,Hui Yang,Wei Xu,Shenghong Ma,Huaipeng Lin,Honguang Zhu,Lixia Liu,Ying Liu,Chen Yang,Yanhui Xu,Shimin Zhao,Dan Ye,Yue Xiong,Kun-Liang Guan,Kun-Liang Guan +14 more
TL;DR: This study suggests that tumor-derived FH and SDH mutations accumulate fumarate and succinate, leading to enzymatic inhibition of multiple α-KG-dependent dioxygenases and consequent alterations of genome-wide histone and DNA methylation.
Journal ArticleDOI
Non-heme Fe(IV)-oxo intermediates.
TL;DR: The observation of non-heme Fe(IV)-oxo intermediates and Fe(II)-containing product(s) complexes with almost identical spectroscopic parameters in the reactions of two distantly related alphaKG-dependent hydroxylases suggests that members of this subfamily follow a conserved mechanism for substrate hydroxyation.
Journal ArticleDOI
Lysine Succinylation Is a Frequently Occurring Modification in Prokaryotes and Eukaryotes and Extensively Overlaps with Acetylation
Brian T. Weinert,Christian Schölz,Sebastian A. Wagner,Vytautas Iesmantavicius,Dan Su,Jeremy A. Daniel,Chunaram Choudhary +6 more
TL;DR: A systems-wide view of succinylation and its dynamic regulation is provided and its extensive overlap with acetylation is shown, indicating that succinylated levels are globally affected by succinyl-CoA concentration.
References
More filters
Journal ArticleDOI
Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
Journal ArticleDOI
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
Journal ArticleDOI
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
Andrew C. R Epstein,Jonathan M. Gleadle,Luke A. McNeill,Kirsty S. Hewitson,J F O'Rourke,David R. Mole,Mridul Mukherji,Eric Metzen,Michael A Wilson,Anu Dhanda,Ya-Min Tian,Norma Masson,Donald L. Hamilton,Panu Jaakkola,Robert Barstead,Jonathan Hodgkin,Patrick H. Maxwell,Christopher W. Pugh,Christopher J. Schofield,Peter J. Ratcliffe +19 more
TL;DR: Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.
Journal ArticleDOI
A Conserved Family of Prolyl-4-Hydroxylases That Modify HIF
TL;DR: In cultured mammalian cells, inappropriate accumulation of HIF caused by forced expression of the HIF-1α subunit under normoxic conditions was attenuated by coexpression of HPH, indicating that HPH is an essential component of the pathway through which cells sense oxygen.
Journal ArticleDOI