4FNH

Crystal structure of IsdI-W66Y in complex with heme

4FNH の概要

• エントリーDOI: 10.2210/pdb4fnh/pdb
• 関連するPDBエントリー: 4FNI
• 分子名称: Heme-degrading monooxygenase isdI, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: alpha/beta barrel, oxidoreductase
• 由来する生物種: Staphylococcus aureus subsp. aureus
• 細胞内の位置: Cytoplasm (By similarity): Q7A827
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27217.69

構造登録者

Ukpabi, G.N.,Murphy, M.E.P. (登録日: 2012-06-19, 公開日: 2012-08-22, 最終更新日: 2023-09-13)

主引用文献

Ukpabi, G.,Takayama, S.J.,Mauk, A.G.,Murphy, M.E.
Inactivation of the heme degrading enzyme IsdI by an active site substitution that diminishes heme ruffling.
J.Biol.Chem., 287:34179-34188, 2012

PubMed Abstract: IsdG and IsdI are paralogous heme degrading enzymes from the bacterium Staphylococcus aureus. Heme bound by these enzymes is extensively ruffled such that the meso-carbons at the sites of oxidation are distorted toward bound oxygen. In contrast, the canonical heme oxygenase family degrades heme that is bound with minimal distortion. Trp-66 is a conserved heme pocket residue in IsdI implicated in heme ruffling. IsdI variants with Trp-66 replaced with residues having less bulky aromatic and alkyl side chains were characterized with respect to catalytic activity, heme ruffling, and electrochemical properties. The heme degradation activity of the W66Y and W66F variants was approximately half that of the wild-type enzyme, whereas the W66L and W66A variants were inactive. A crystal structure and NMR spectroscopic analysis of the W66Y variant reveals that heme binds to this enzyme with less heme ruffling than observed for wild-type IsdI. The reduction potential of this variant (-96 ± 7 mV versus standard hydrogen electrode) is similar to that of wild-type IsdI (-89 ± 7 mV), so we attribute the diminished activity of this variant to the diminished heme ruffling observed for heme bound to this enzyme and conclude that Trp-66 is required for optimal catalytic activity.

PubMed: 22891243
DOI: 10.1074/jbc.M112.393249

実験手法

X-RAY DIFFRACTION (1.9 Å)