3G5K

Structure and activity of human mitochondrial peptide deformylase, a novel cancer target

Summary for 3G5K

• Entry DOI: 10.2210/pdb3g5k/pdb
• Related: 1G2A 1IX1 1LQW 1ZY0 1ZY1 3G5P
• Descriptor: Peptide deformylase, mitochondrial, ACTINONIN, COBALT (II) ION, ... (4 entities in total)
• Functional Keywords: peptide deformylase, actinonin, hydrolase, iron, metal-binding, mitochondrion, protein biosynthesis, transit peptide
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion (Potential): Q9HBH1
• Total number of polymer chains: 4
• Total formula weight: 84389.78

Authors

Escobar-Alvarez, S.,Goldgur, Y.,Yang, G.,Ouerfelli, O.,Li, Y.,Scheinberg, D.A. (deposition date: 2009-02-05, release date: 2009-04-07, Last modification date: 2023-09-06)

Primary citation

Escobar-Alvarez, S.,Goldgur, Y.,Yang, G.,Ouerfelli, O.,Li, Y.,Scheinberg, D.A.
Structure and activity of human mitochondrial peptide deformylase, a novel cancer target
J.Mol.Biol., 387:1211-1228, 2009

PubMed 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.

PubMed: 19236878
DOI: 10.1016/j.jmb.2009.02.032

Experimental method

X-RAY DIFFRACTION (1.7 Å)