Journal article
Structural analysis of cofactor binding for a prolyl 4-hydroxylase from the pathogenic bacterium Bacillus anthracis
Acta crystallographica. Section D, Structural biology, Vol.72(5), pp.675-681
05/2016
DOI: 10.1107/S2059798316004198
PMID: 27139630
Abstract
The prolyl 4-hydroxylases (P4Hs) are mononuclear nonheme iron enzymes that catalyze the formation of 4R-hydroxyproline from many different substrates, with various biological implications. P4H is a key player in collagen accumulation, which has implications in fibrotic disorders. The stabilization of collagen triple-helical structure via prolyl hydroxylation is the rate-limiting step in collagen biosynthesis, and therefore P4H has been extensively investigated as a potential therapeutic target of fibrotic disease. Understanding how these enzymes recognize cofactors and substrates is important and will aid in the future design of inhibitors of P4H. In this article, X-ray crystal structures of a metallocofactor-and alpha-ketoglutarate (alpha KG)-bound form of P4H from Bacillus anthracis (BaP4H) are reported. Structures of BaP4H were solved at 1.63 and 2.35 angstrom resolution and contained a cadmium ion and alpha KG bound in the active site. The alpha KG-Cd-BaP4H ternary complex reveals conformational changes of conserved residues upon the binding of metal ion and alpha KG, resulting in a closed active-site configuration required for dioxygen, substrate binding and catalysis.
Details
- Title: Subtitle
- Structural analysis of cofactor binding for a prolyl 4-hydroxylase from the pathogenic bacterium Bacillus anthracis
- Creators
- Nicholas J. Schnicker - University of IowaMishtu Dey - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Acta crystallographica. Section D, Structural biology, Vol.72(5), pp.675-681
- Publisher
- Int Union Crystallography
- DOI
- 10.1107/S2059798316004198
- PMID
- 27139630
- ISSN
- 2059-7983
- eISSN
- 2059-7983
- Number of pages
- 7
- Grant note
- University of Iowa College of Liberal Arts and Sciences US Department of Energy; United States Department of Energy (DOE)
- Language
- English
- Date published
- 05/2016
- Academic Unit
- Molecular Physiology and Biophysics; Chemistry; Medicine Administration
- Record Identifier
- 9984622755602771
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