4G1B

X-ray structure of yeast flavohemoglobin in complex with econazole

4G1B の概要

• エントリーDOI: 10.2210/pdb4g1b/pdb
• 分子名称: Flavohemoglobin, PROTOPORPHYRIN IX CONTAINING FE, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: three domains: globin fold, antiparallel beta-barrel, alpha/beta fold, resp., hem, fad, econazole, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 185999.80

構造登録者

El Hammi, E.,Warkentin, E.,Demmer, U.,Baciou, L.,Ermler, U. (登録日: 2012-07-10, 公開日: 2012-11-14, 最終更新日: 2024-11-20)

主引用文献

El Hammi, E.,Warkentin, E.,Demmer, U.,Marzouki, N.M.,Ermler, U.,Baciou, L.
Active site analysis of yeast flavohemoglobin based on its structure with a small ligand or econazole.
Febs J., 279:4565-4575, 2012

PubMed Abstract: Flavohemoglobins (flavoHbs) serve various microorganisms as the major protective enzymes against NO˙-mediated toxicity. FlavoHbs dominantly function as an NO˙ dioxygenase (O2+ NO→ NO3 -), the required electron being shuttled from NAD(P)H via FAD to the heme iron. The X-ray structures of the flavoHb from Saccharomyces cerevisae presented in complex with an unknown small ligand (Yhb) and with econazole (Yhb(E) ) at 2.1 and 3.0 Å resolutions, respectively, reveal a high architectural accordance between prokaryotic and eukaryotic family members. The active site is characterized by a proximal heme side with a strictly conserved histidine, glutamate and tyrosine triad and a highly variable distal heme side with helix shifts up to 10 Å mainly dependent on the presence/absence and size of the bound ligand. In yeast flavoHb, the small heme iron ligand adjusts a catalytically productive active site geometry that reliably suggests the NO and O(2) binding site. O(2) is activated by its ligation to an electron-rich heme iron and a hydrogen bond to Tyr29 and Gln53. High active site similarities between eukaryotic Yhb and bacterial single-domain globins argue for identical biochemical reactions. Binding of the bulky econazole implies a large-scale induced-fit process concerning, in particular, an outwards shift of helices B and E to increase the active site pocket. Yeast Yhb and Ralstonia eutropha flavoHb both structurally studied in complex with econazole indicate conformational differences between the inhibitors and the polypeptide primarily caused by stable binding of a phospholipid to the latter and by distinct loop D structures.

PubMed: 23095020
DOI: 10.1111/febs.12043

実験手法

X-RAY DIFFRACTION (3 Å)