2XWL

Crystal structure of IspD from Mycobacterium smegmatis in complex with CTP and Mg

2XWL の概要

• エントリーDOI: 10.2210/pdb2xwl/pdb
• 関連するPDBエントリー: 2XWM 2XWN
• 分子名称: 2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE CYTIDYLYLTRANSFERASE, MAGNESIUM ION, CYTIDINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: transferase, mep pathway
• 由来する生物種: MYCOBACTERIUM SMEGMATIS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46350.63

構造登録者

Bjorkelid, C.,Bergfors, T.,Unge, T.,Jones, T.A. (登録日: 2010-11-04, 公開日: 2011-04-27, 最終更新日: 2023-12-20)

主引用文献

Bjorkelid, C.,Bergfors, T.,Henriksson, L.M.,Stern, A.L.,Unge, T.,Mowbray, S.L.,Jones, T.A.
Structural and Functional Studies on Mycobacterial Ispd Enzymes
Acta Crystallogr.,Sect.D, 67:403-, 2011

PubMed Abstract: A number of pathogens, including the causative agents of tuberculosis and malaria, synthesize isopentenyl diphosphate via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway rather than the classical mevalonate pathway found in humans. As part of a structure-based drug-discovery program against tuberculosis, IspD, the enzyme that carries out the third step in the MEP pathway, was targeted. Constructs of both the Mycobacterium smegmatis and the Mycobacterium tuberculosis enzymes that were suitable for structural and inhibitor-screening studies were engineered. Two crystal structures of the M. smegmatis enzyme were produced, one in complex with CTP and the other in complex with CMP. In addition, the M. tuberculosis enzyme was crystallized in complex with CTP. Here, the structure determination and crystallographic refinement of these crystal forms and the enzymatic characterization of the M. tuberculosis enzyme construct are reported. A comparison with known IspD structures allowed the definition of the structurally conserved core of the enzyme. It indicates potential flexibility in the enzyme and in particular in areas close to the active site. These well behaved constructs provide tools for future target-based screening of potential inhibitors. The conserved nature of the extended active site suggests that any new inhibitor will potentially exhibit broad-spectrum activity.

PubMed: 21543842
DOI: 10.1107/S0907444911006160

実験手法

X-RAY DIFFRACTION (1.49 Å)