3B03

Crystal structure of Sulfolobus shibatae isopentenyl diphosphate isomerase in complex with vIPP.

3B03 の概要

• エントリーDOI: 10.2210/pdb3b03/pdb
• 関連するPDBエントリー: 3B04 3B05 3B06
• 分子名称: Isopentenyl-diphosphate delta-isomerase, 1-deoxy-1-[(4aR)-4a-[(2Z)-2-(2-{[(S)-hydroxy(phosphonooxy)phosphoryl]oxy}ethyl)but-2-en-1-yl]-7,8-dimethyl-2,4-dioxo-3,4,4a,5-tetrahydrobenzo[g]pteridin-10(2H)-yl]-5-O-phosphono-D-ribitol, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: type 2, idi, fmn, isopentenyl diphosphate isomerase, vipp, isomerase
• 由来する生物種: Sulfolobus shibatae
• 細胞内の位置: Cytoplasm (By similarity): P61615
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 164842.03

構造登録者

Unno, H.,Nagai, T.,Hemmi, H. (登録日: 2011-06-03, 公開日: 2011-11-02, 最終更新日: 2024-03-13)

主引用文献

Nagai, T.,Unno, H.,Janczak, M.W.,Yoshimura, T.,Poulter, C.D.,Hemmi, H.
Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl diphosphate isomerase by active-site-directed inhibitors.
Proc.Natl.Acad.Sci.USA, 108:20461-20466, 2011

PubMed Abstract: Evidence for an unusual catalysis of protonation/deprotonation by a reduced flavin mononucleotide cofactor is presented for type-2 isopentenyl diphosphate isomerase (IDI-2), which catalyzes isomerization of the two fundamental building blocks of isoprenoid biosynthesis, isopentenyl diphosphate and dimethylallyl diphosphate. The covalent adducts formed between irreversible mechanism-based inhibitors, 3-methylene-4-penten-1-yl diphosphate or 3-oxiranyl-3-buten-1-yl diphosphate, and the flavin cofactor were investigated by X-ray crystallography and UV-visible spectroscopy. Both the crystal structures of IDI-2 binding the flavin-inhibitor adduct and the UV-visible spectra of the adducts indicate that the covalent bond is formed at C4a of flavin rather than at N5, which had been proposed previously. In addition, the high-resolution crystal structures of IDI-2-substrate complexes and the kinetic studies of new mutants confirmed that only the flavin cofactor can catalyze protonation of the substrates and suggest that N5 of flavin is most likely to be involved in proton transfer. These data provide support for a mechanism where the reduced flavin cofactor acts as a general acid/base catalyst and helps stabilize the carbocationic intermediate formed by protonation.

PubMed: 22158896
DOI: 10.1073/pnas.1115749108

実験手法

X-RAY DIFFRACTION (2.2 Å)