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Bioorg Med Chem. 2013 Jun 15;21(12):3597-601. doi: 10.1016/j.bmc.2013.04.057. Epub 2013 Apr 30.

Bioavailable affinity label for collagen prolyl 4-hydroxylase.

Author information

1
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA.

Abstract

Collagen is the most abundant protein in animals. Its prevalent 4-hydroxyproline residues contribute greatly to its conformational stability. The hydroxyl groups arise from a post-translational modification catalyzed by the nonheme iron-dependent enzyme, collagen prolyl 4-hydroxylase (P4H). Here, we report that 4-oxo-5,6-epoxyhexanoate, a mimic of the α-ketoglutarate co-substrate, inactivates human P4H. The inactivation installs a ketone functionality in P4H, providing a handle for proteomic experiments. Caenorhabditis elegans exposed to the esterified epoxy ketone displays the phenotype of a worm lacking P4H. Thus, this affinity label can be used to mediate collagen stability in an animal, as is desirable in the treatment of a variety of fibrotic diseases.

PMID:
23702396
PMCID:
PMC3723383
DOI:
10.1016/j.bmc.2013.04.057
[Indexed for MEDLINE]
Free PMC Article

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