Reference : Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and ste...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/26337
Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and stereoselectivity of prolyl hydroxylases.
English
Horita, Shoichiro [> >]
Scotti, John S. [> >]
Thinnes, Cyrille [University of Oxford > Department of Chemistry]
Mottaghi-Taromsari, Yousef S. [> >]
Thalhammer, Armin [> >]
Ge, Wei [> >]
Aik, Weishen [> >]
Loenarz, Christoph [> >]
Schofield, Christopher J. [> >]
McDonough, Michael A. [> >]
2015
Structure (London, England : 1993)
23
4
639-52
Yes (verified by ORBilu)
International
0969-2126
1878-4186
United States
[en] Amino Acid Sequence ; Binding Sites ; Carrier Proteins/antagonists & inhibitors/chemistry/metabolism ; Humans ; Molecular Docking Simulation ; Molecular Sequence Data ; Nuclear Proteins/antagonists & inhibitors/chemistry/metabolism ; Prolyl-Hydroxylase Inhibitors/pharmacology ; Protein Binding ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae Proteins/antagonists & inhibitors/chemistry/metabolism ; Substrate Specificity
[en] Post-translational ribosomal protein hydroxylation is catalyzed by 2-oxoglutarate (2OG) and ferrous iron dependent oxygenases, and occurs in prokaryotes and eukaryotes. OGFOD1 catalyzes trans-3 prolyl hydroxylation at Pro62 of the small ribosomal subunit protein uS12 (RPS23) and is conserved from yeasts to humans. We describe crystal structures of the human uS12 prolyl 3-hydroxylase (OGFOD1) and its homolog from Saccharomyces cerevisiae (Tpa1p): OGFOD1 in complex with the broad-spectrum 2OG oxygenase inhibitors; N-oxalylglycine (NOG) and pyridine-2,4-dicarboxylate (2,4-PDCA) to 2.1 and 2.6 A resolution, respectively; and Tpa1p in complex with NOG, 2,4-PDCA, and 1-chloro-4-hydroxyisoquinoline-3-carbonylglycine (a more selective prolyl hydroxylase inhibitor) to 2.8, 1.9, and 1.9 A resolution, respectively. Comparison of uS12 hydroxylase structures with those of other prolyl hydroxylases, including the human hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs), reveals differences between the prolyl 3- and prolyl 4-hydroxylase active sites, which can be exploited for developing selective inhibitors of the different subfamilies.
http://hdl.handle.net/10993/26337
Copyright (c) 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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