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PDBsum entry 3itq
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Oxidoreductase
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PDB id
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3itq
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References listed in PDB file
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Key reference
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Title
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Crystal structure of prolyl 4-Hydroxylase from bacillus anthracis.
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Authors
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M.A.Culpepper,
E.E.Scott,
J.Limburg.
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Ref.
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Biochemistry, 2010,
49,
124-133.
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PubMed id
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Abstract
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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 previous
structures of P4H enzymes are monomers, B. anthracis P4H forms an alpha(2)
homodimer and suggests residues important for interactions between the alpha(2)
subunits of alpha(2)beta(2) human collagen P4H. Thus, the anthrax P4H structure
provides insight into the structure and function of the alpha-subunit of human
P4H, which may aid in the development of selective inhibitors of the human P4H
enzyme involved in fibrotic disease.
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