3G5P

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

3G5P の概要

• エントリーDOI: 10.2210/pdb3g5p/pdb
• 関連するPDBエントリー: 1G2A 1IX1 1LQW 1ZY0 1ZY1 3G5K
• 分子名称: Peptide deformylase, mitochondrial, COBALT (II) ION, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: peptide deformylase, human, mitochondria, hydrolase, iron, metal-binding, mitochondrion, protein biosynthesis, transit peptide
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion (Potential): Q9HBH1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83607.56

構造登録者

Escobar-Alvarez, S.,Goldgur, Y.,Yang, G.,Ouerfelli, O.,Li, Y.,Scheinberg, D.A. (登録日: 2009-02-05, 公開日: 2009-04-07, 最終更新日: 2023-09-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.7 Å)