1OX4

TOWARDS UNDERSTANDING THE MECHANISM OF THE COMPLEX CYCLIZATION REACTION CATALYZED BY IMIDAZOLE GLYCEROPHOSPHATE SYNTHASE

1OX4 の概要

• エントリーDOI: 10.2210/pdb1ox4/pdb
• 関連するPDBエントリー: 1JVN 1OX4 1OX5 1OX6
• 分子名称: Imidazole glycerol phosphate synthase hisHF, SULFATE ION, NICKEL (II) ION, ... (6 entities in total)
• 機能のキーワード: complex cyclization; imidazole glycerophosphate synthase, transferase, lyase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123841.02

構造登録者

Chaudhuri, B.N.,Smith, J.L. (登録日: 2003-04-01, 公開日: 2003-06-17, 最終更新日: 2023-08-16)

主引用文献

Chaudhuri, B.N.,Lange, C.,Myers, R.S.,Davisson, V.J.,Smith, J.L.
Towards Understanding the Mechanism of the Complex Cyclization Reaction Catalyzed by Imidazole Glycerophosphate Synthase: Crystal Structures of a Ternary Complex and the Free Enzyme
Biochemistry, 42:7003-7012, 2003

PubMed Abstract: Imidazole glycerol phosphate synthase catalyzes formation of the imidazole ring in histidine biosynthesis. The enzyme is also a glutamine amidotransferase, which produces ammonia in a glutaminase active site and channels it through a 30-A internal tunnel to a cyclase active site. Glutaminase activity is impaired in the resting enzyme, and stimulated by substrate binding in the cyclase active site. The signaling mechanism was investigated in the crystal structure of a ternary complex in which the glutaminase active site was inactivated by a glutamine analogue and the unstable cyclase substrate was cryo-trapped in the active site. The orientation of N(1)-(5'-phosphoribulosyl)-formimino-5-aminoimidazole-4-carboxamide ribonucleotide in the cyclase active site implicates one side of the cyclase domain in signaling to the glutaminase domain. This side of the cyclase domain contains the interdomain hinge. Two interdomain hydrogen bonds, which do not exist in more open forms of the enzyme, are proposed as molecular signals. One hydrogen bond connects the cyclase domain to the substrate analogue in the glutaminase active site. The second hydrogen bond connects to a peptide that forms an oxyanion hole for stabilization of transient negative charge during glutamine hydrolysis. Peptide rearrangement induced by a fully closed domain interface is proposed to activate the glutaminase by unblocking the oxyanion hole. This interpretation is consistent with biochemical results [Myers, R. S., et al., (2003) Biochemistry 42, 7013-7022, the accompanying paper in this issue] and with structures of the free enzyme and a binary complex with a second glutamine analogue.

PubMed: 12795595
DOI: 10.1021/bi034320h

実験手法

X-RAY DIFFRACTION (2.5 Å)