Abstract |
Peptide deformylase proteins (PDFs) participate in the N-terminal methionine excision pathway of newly synthesized peptides. We show that the human PDF (HsPDF) can deformylate its putative substrates derived from mitochondrial DNA-encoded proteins. The first structural model of a mammalian PDF (1.7 A), HsPDF, shows a dimer with conserved topology of the catalytic residues and fold as non-mammalian PDFs. The HsPDF C-terminus topology and the presence of a helical loop (H2 and H3), however, shape a characteristic active site entrance. The structure of HsPDF bound to the peptidomimetic inhibitor actinonin (1.7 A) identified the substrate-binding site. A defined S1' pocket, but no S2' or S3' substrate-binding pockets, exists. A conservation of PDF- actinonin interaction across PDFs was observed. Despite the lack of true S2' and S3' binding pockets, confirmed through peptide binding modeling, enzyme kinetics suggest a combined contribution from P2'and P3' positions of a formylated peptide substrate to turnover.
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Authors | Sindy Escobar-Alvarez, Yehuda Goldgur, Guangli Yang, Ouathek Ouerfelli, Yueming Li, David A Scheinberg |
Journal | Journal of molecular biology
(J Mol Biol)
Vol. 387
Issue 5
Pg. 1211-28
(Apr 17 2009)
ISSN: 1089-8638 [Electronic] Netherlands |
PMID | 19236878
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- DNA, Mitochondrial
- Oligopeptides
- Recombinant Proteins
- Amidohydrolases
- peptide deformylase
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Topics |
- Amidohydrolases
(antagonists & inhibitors, chemistry, genetics, metabolism)
- Amino Acid Sequence
- Base Sequence
- Catalytic Domain
- Conserved Sequence
- Crystallography, X-Ray
- DNA Primers
(genetics)
- DNA, Mitochondrial
(genetics)
- Dimerization
- Humans
- In Vitro Techniques
- Kinetics
- Mitochondria
(enzymology)
- Models, Molecular
- Molecular Sequence Data
- Neoplasms
(drug therapy, enzymology)
- Oligopeptides
(chemistry, genetics)
- Protein Folding
- Protein Structure, Quaternary
- Recombinant Proteins
(chemistry, genetics, metabolism)
- Sequence Homology, Amino Acid
- Static Electricity
- Substrate Specificity
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