6E2U

MDDEF in complex with MVAPP, AMPPCP and Magnesium

6E2U の概要

• エントリーDOI: 10.2210/pdb6e2u/pdb
• 分子名称: Mevalonate diphosphate decarboxylase, (3R)-3-HYDROXY-5-{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}-3-METHYLPENTANOIC ACID, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: mevalonate diphosphate decarboxylase, lyase
• 由来する生物種: Enterococcus faecalis (Streptococcus faecalis)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40113.99

構造登録者

Stauffacher, C.V.,Chen, C.-L. (登録日: 2018-07-12, 公開日: 2020-01-15, 最終更新日: 2023-10-11)

主引用文献

Chen, C.L.,Paul, L.N.,Mermoud, J.C.,Steussy, C.N.,Stauffacher, C.V.
Visualizing the enzyme mechanism of mevalonate diphosphate decarboxylase.
Nat Commun, 11:3969-3969, 2020

PubMed Abstract: Mevalonate diphosphate decarboxylases (MDDs) catalyze the ATP-dependent-Mg-decarboxylation of mevalonate-5-diphosphate (MVAPP) to produce isopentenyl diphosphate (IPP), which is essential in both eukaryotes and prokaryotes for polyisoprenoid synthesis. The substrates, MVAPP and ATP, have been shown to bind sequentially to MDD. Here we report crystals in which the enzyme remains active, allowing the visualization of conformational changes in Enterococcus faecalis MDD that describe sequential steps in an induced fit enzymatic reaction. Initial binding of MVAPP modulates the ATP binding pocket with a large loop movement. Upon ATP binding, a phosphate binding loop bends over the active site to recognize ATP and bring the molecules to their catalytically favored configuration. Positioned substrates then can chelate two Mg ions for the two steps of the reaction. Closure of the active site entrance brings a conserved lysine to trigger dissociative phosphoryl transfer of γ-phosphate from ATP to MVAPP, followed by the production of IPP.

PubMed: 32769976
DOI: 10.1038/s41467-020-17733-0

実験手法

X-RAY DIFFRACTION (2.05 Å)