2fp0
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human ADP-ribosylhydrolase 3
OverviewOverview
Posttranslational modifications are used by cells from all kingdoms of, life to control enzymatic activity and to regulate protein function. For, many cellular processes, including DNA repair, spindle function, and, apoptosis, reversible mono- and polyADP-ribosylation constitutes a very, important regulatory mechanism. Moreover, many pathogenic bacteria secrete, toxins which ADP-ribosylate human proteins, causing diseases such as, whooping cough, cholera, and diphtheria. Whereas the 3D structures of, numerous ADP-ribosylating toxins and related mammalian enzymes have been, elucidated, virtually nothing is known about the structure of protein, de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human, ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3, constitutes the archetype of an all-alpha-helical protein fold and, provides insights into the reversibility of protein ADP-ribosylation. Two, magnesium ions flanked by highly conserved amino acids pinpoint the, active-site crevice. Recombinant hARH3 binds free ADP-ribose with, micromolar affinity and efficiently de-ADP-ribosylates poly- but not, monoADP-ribosylated proteins. Docking experiments indicate a possible, binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our, results underscore the importance of endogenous ADP-ribosylation cycles, and provide a basis for structure-based design of ADP-ribosylhydrolase, inhibitors.
About this StructureAbout this Structure
2FP0 is a Single protein structure of sequence from Homo sapiens with MG as ligand. Full crystallographic information is available from OCA.
ReferenceReference
The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation., Mueller-Dieckmann C, Kernstock S, Lisurek M, von Kries JP, Haag F, Weiss MS, Koch-Nolte F, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15026-31. Epub 2006 Oct 2. PMID:17015823
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