Reference : Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and ste...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and stereoselectivity of prolyl hydroxylases.
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. [> >]
Structure (London, England : 1993)
Yes (verified by ORBilu)
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.
Copyright (c) 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

There is no file associated with this reference.

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.