2E03

Crystal structure of NQ67E mutant of yeast bleomycin hydrolase

2E03 の概要

• エントリーDOI: 10.2210/pdb2e03/pdb
• 関連するPDBエントリー: 2DZY 2DZZ 2E00 2E01 2E02
• 分子名称: Cysteine proteinase 1 (2 entities in total)
• 機能のキーワード: bleomycin hydrolase, thiol protease, c1 proteas, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Isoform Cytoplasmic: Cytoplasm. Isoform Mitochondrial: Mitochondrion: Q01532
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52427.64

構造登録者

O'Farrell, P.A.,Joshua-Tor, L. (登録日: 2006-10-01, 公開日: 2007-08-14, 最終更新日: 2023-10-25)

主引用文献

O'Farrell, P.A.,Joshua-Tor, L.
Mutagenesis and crystallographic studies of the catalytic residues of the papain family protease bleomycin hydrolase: new insights into active-site structure
Biochem.J., 401:421-428, 2007

PubMed Abstract: Bleomycin hydrolase (BH) is a hexameric papain family cysteine protease which is involved in preparing peptides for antigen presentation and has been implicated in tumour cell resistance to bleomycin chemotherapy. Structures of active-site mutants of yeast BH yielded unexpected results. Replacement of the active-site asparagine with alanine, valine or leucine results in the destabilization of the histidine side chain, demonstrating unambiguously the role of the asparagine residue in correctly positioning the histidine for catalysis. Replacement of the histidine with alanine or leucine destabilizes the asparagine position, indicating a delicate arrangement of the active-site residues. In all of the mutants, the C-terminus of the protein, which lies in the active site, protrudes further into the active site. All mutants were compromised in their catalytic activity. The structures also revealed the importance of a tightly bound water molecule which stabilizes a loop near the active site and which is conserved throughout the papain family. It is displaced in a number of the mutants, causing destabilization of this loop and a nearby loop, resulting in a large movement of the active-site cysteine. The results imply that this water molecule plays a key structural role in this family of enzymes.

PubMed: 17007609
DOI: 10.1042/BJ20060641

実験手法

X-RAY DIFFRACTION (2.13 Å)