5HV0

Structural Analysis of Cofactor Binding of a Prolyl 4-Hydroxylase from the Pathogenic Bacterium Bacillus anthracis

Summary for 5HV0

• Entry DOI: 10.2210/pdb5hv0/pdb
• Related: 5HV4
• Descriptor: Prolyl 4-Hydroxylase, CADMIUM ION, 2-OXOGLUTARIC ACID, ... (6 entities in total)
• Functional Keywords: p4h, dioxygenase, cupin, fe(ii)/alpha-ketoglutarate, oxidoreductase
• Biological source: Bacillus anthracis
• Total number of polymer chains: 2
• Total formula weight: 51506.42

Authors

Schnicker, N.J.,Dey, M. (deposition date: 2016-01-28, release date: 2016-05-04, Last modification date: 2023-09-27)

Primary citation

Schnicker, N.J.,Dey, M.
Structural analysis of cofactor binding for a prolyl 4-hydroxylase from the pathogenic bacterium Bacillus anthracis.
Acta Crystallogr D Struct Biol, 72:675-681, 2016

PubMed 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 α-ketoglutarate (αKG)-bound form of P4H from Bacillus anthracis (BaP4H) are reported. Structures of BaP4H were solved at 1.63 and 2.35 Å resolution and contained a cadmium ion and αKG bound in the active site. The αKG-Cd-BaP4H ternary complex reveals conformational changes of conserved residues upon the binding of metal ion and αKG, resulting in a closed active-site configuration required for dioxygen, substrate binding and catalysis.

PubMed: 27139630
DOI: 10.1107/S2059798316004198

Experimental method

X-RAY DIFFRACTION (1.63 Å)