9IMR

Crystal structure of geranylgeranyl pyrophosphate synthase Rv0562 from Mycobacterium tuberculosis in complex with IPP

9IMR の概要

• エントリーDOI: 10.2210/pdb9imr/pdb
• 分子名称: Nonaprenyl diphosphate synthase, 3-METHYLBUT-3-ENYL TRIHYDROGEN DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: geranylgeranyl pyrophosphate synthase, isoprenyl diphosphate synthases, terpenoids, transferase
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73085.51

構造登録者

Wang, Q.,Yang, Y.,Chen, C.-C.,Guo, R.-T. (登録日: 2024-07-04, 公開日: 2025-07-09, 最終更新日: 2025-08-06)

主引用文献

Wang, Q.,Yang, Y.,He, B.,Huang, J.W.,Kuo, C.J.,Chen, C.C.,Guo, R.T.
Structural insight of a bi-functional isoprenyl diphosphate synthase Rv0562 from Mycobacterium tuberculosis.
Int.J.Biol.Macromol., 318:145171-145171, 2025

PubMed Abstract: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Mtb uses MK-9(II-H), which consists of an isoprenyl side chain containing nine isoprene units, with one being hydrogenated in the β-position, as an essential element in the electron transport system. Rv0562 that can operate geranylgeranyl diphosphate synthase (GGPPs) activity catalyzes the synthesis of MK-9(II-H) by condensing one molecule of dimethylallyl diphosphate (DMAPP) with eight molecules of isopentenyl diphosphate (IPP) to form a C long-chain isoprenoid product. In this study, the structures of Rv0562 were determined in the apo-form at a resolution of 2.54 Å and in complex with IPP and Mg at a resolution of 1.89 Å, revealing detailed interactions between the enzyme and substrates. Moreover, the crystal structure of the Rv0562-DM variant was determined at 2.27 Å resolution in complex with polyethylene glycol (PEG), which occupies the substrate binding tunnel, mimicking the long-chain product. The chain length determination mechanism of Rv0562 is also probed through mutagenesis experiments. The obtained structures help us understand how Rv0562 catalyzes isoprenyl chain elongation, showing implications in developing new anti-Mtb treatments.

PubMed: 40513738
DOI: 10.1016/j.ijbiomac.2025.145171

実験手法

X-RAY DIFFRACTION (1.89 Å)