6RJN

Crystal structure of a Fungal Catalase at 2.3 Angstroms

6RJN の概要

• エントリーDOI: 10.2210/pdb6rjn/pdb
• 分子名称: Catalase, PROTOPORPHYRIN IX CONTAINING FE, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (10 entities in total)
• 機能のキーワード: pichia pastoris, catalase, heme, nadp, oxidoreductase
• 由来する生物種: Komagataella pastoris
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 240222.79

構造登録者

Gomez, S.,Navas-Yuste, S.,Payne, A.M.,Rivera, W.,Lopez-Estepa, M.,Brangbour, C.,Fulla, D.,Juanhuix, J.,Fernandez, F.J.,Vega, M.C. (登録日: 2019-04-28, 公開日: 2020-03-04, 最終更新日: 2024-01-24)

主引用文献

Gomez, S.,Navas-Yuste, S.,Payne, A.M.,Rivera, W.,Lopez-Estepa, M.,Brangbour, C.,Fulla, D.,Juanhuix, J.,Fernandez, F.J.,Vega, M.C.
Peroxisomal catalases from the yeasts Pichia pastoris and Kluyveromyces lactis as models for oxidative damage in higher eukaryotes.
Free Radic. Biol. Med., 141:279-290, 2019

PubMed Abstract: Catalases are among the main scavengers of reactive oxygen species (ROS) present in the peroxisome, thereby preventing oxidative cellular and tissular damage. In human, multiple diseases are associated with malfunction of these organelles, which causes accumulation of ROS species and consequently the inefficient detoxification of cells. Despite intense research, much remains to be clarified about the precise molecular role of catalase in cellular homeostasis. Yeast peroxisomes and their peroxisomal catalases have been used as eukaryotic models for oxidative metabolism, ROS generation and detoxification, and associated pathologies. In order to provide reliable models for oxidative metabolism research, we have determined the high-resolution crystal structures of peroxisomal catalase from two important biotechnology and basic biology yeast models, Pichia pastoris and Kluyveromyces lactis. We have performed an extensive functional, biochemical and stability characterization of both enzymes in order to establish their differential activity profiles. Furthermore, we have analyzed the role of the peroxisomal catalase under study in the survival of yeast to oxidative burst challenges combining methanol, water peroxide, and sodium chloride. Interestingly, whereas catalase activity was induced 200-fold upon challenging the methylotrophic P. pastoris cells with methanol, the increase in catalase activity in the non-methylotrophic K. lactis was only moderate. The inhibitory effect of sodium azide and β-mercaptoethanol over both catalases was analyzed, establishing IC50 values for both compounds that are consistent with an elevated resistance of both enzymes toward these inhibitors. Structural comparison of these two novel catalase structures allows us to rationalize the differential susceptibility to inhibitors and oxidative bursts. The inherent worth and validity of the P. pastoris and K. lactis yeast models for oxidative damage will be strengthened by the availability of reliable structural-functional information on these enzymes, which are central to our understanding of peroxisomal response toward oxidative stress.

PubMed: 31238127
DOI: 10.1016/j.freeradbiomed.2019.06.025

実験手法

X-RAY DIFFRACTION (2.295 Å)