Crystal structure of prolyl 4-hydroxylase from Bacillus anthracis.

Biochemistry
Megen A CulpepperJulian Limburg

Abstract

Prolyl 4-hydroxylases (P4H) catalyze the post-translational hydroxylation of proline residues and play a role in collagen production, hypoxia response, and cell wall development. P4Hs belong to the group of Fe(II)/alphaKG oxygenases and require Fe(II), alpha-ketoglutarate (alphaKG), and O(2) for activity. We report the 1.40 A structure of a P4H from Bacillus anthracis, the causative agent of anthrax, whose immunodominant exosporium protein BclA contains collagen-like repeat sequences. The structure reveals the double-stranded beta-helix core fold characteristic of Fe(II)/alphaKG oxygenases. This fold positions Fe-binding and alphaKG-binding residues in what is expected to be catalytically competent orientations and is consistent with proline peptide substrate binding at the active site mouth. Comparisons of the anthrax P4H structure with Cr P4H-1 structures reveal similarities in a peptide surface groove. However, sequence and structural comparisons suggest differences in conformation of adjacent loops may change the interaction with peptide substrates. These differences may be the basis of a substantial disparity between the K(M) values for the Cr P4H-1 compared to the anthrax and human P4H enzymes. Additionally, while previou...Continue Reading

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Citations

Jan 24, 2013·Infection and Immunity·Cristine G CamposPeggy A Cotter
Sep 15, 2015·Biochemistry·James E LongbothamNigel S Scrutton
Jan 18, 2014·Journal of Structural Biology·Zhuoxin YuBarbara Brodsky
May 4, 2016·Acta Crystallographica. Section D, Structural Biology·Nicholas J Schnicker, Mishtu Dey
Mar 24, 2017·Journal of the American Chemical Society·Vasiliki E FadouloglouMichael Kokkinidis
Mar 5, 2010·Critical Reviews in Biochemistry and Molecular Biology·Kelly L Gorres, Ronald T Raines
Apr 30, 2016·The Journal of Biological Chemistry·Nicholas J Schnicker, Mishtu Dey

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