3ZR4

STRUCTURAL EVIDENCE FOR AMMONIA TUNNELING ACROSS THE (BETA-ALPHA)8 BARREL OF THE IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE BIENZYME COMPLEX

3ZR4 の概要

• エントリーDOI: 10.2210/pdb3zr4/pdb
• 関連するPDBエントリー: 1GPW 1K9V 1KXJ 1THF 1VH7 2A0N 2W6R 2WJZ
• 分子名称: IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE SUBUNIT HISF, IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE SUBUNIT HISH, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: THERMOTOGA MARITIMA; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 153590.25

構造登録者

Vega, M.C.,Kuper, J.,Haeger, M.C.,Mohrlueder, J.,Marquardt, S.,Sterner, R.,Wilmanns, M. (登録日: 2011-06-13, 公開日: 2012-10-03, 最終更新日: 2023-12-20)

主引用文献

List, F.,Vega, M.C.,Razeto, A.,Hager, M.C.,Sterner, R.,Wilmanns, M.
Catalysis Uncoupling in a Glutamine Amidotransferase Bienzyme by Unblocking the Glutaminase Active Site.
Chem.Biol., 19:1589-, 2012

PubMed Abstract: Nitrogen is incorporated into various metabolites by multifunctional glutamine amidotransferases via reactive ammonia generated by glutaminase hydrolysis of glutamine. Although this process is generally tightly regulated by subsequent synthase activity, little is known about how the glutaminase is inhibited in the absence of an activating signal. Here, we use imidazoleglycerolphosphate synthase as a model to investigate the mechanism of glutaminase regulation. A structure of the bienzyme-glutamine complex reveals that the glutaminase active site is in a catalysis-competent conformation but the ammonia pathway toward the synthase active site is blocked. Mutation of two residues blocking the pathway leads to a complete uncoupling of the two reactions and to a 2800-fold amplification of glutaminase activity. Our data advance the understanding of coupling enzymatic activities in glutamine amidotransferases and raise hypotheses of the underlying molecular mechanism.

PubMed: 23261602
DOI: 10.1016/J.CHEMBIOL.2012.10.012

実験手法

X-RAY DIFFRACTION (2.41 Å)