2GEK

Crystal Structure of phosphatidylinositol mannosyltransferase (PimA) from Mycobacterium smegmatis in complex with GDP

2GEK の概要

• エントリーDOI: 10.2210/pdb2gek/pdb
• 関連するPDBエントリー: 2GEJ
• 分子名称: PHOSPHATIDYLINOSITOL MANNOSYLTRANSFERASE (PimA), GUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: gt4 glycosyltransferase, mannosyltransferase, rossmann fold, binary complex, transferase
• 由来する生物種: Mycobacterium smegmatis
• 細胞内の位置: Cell membrane; Single-pass membrane protein (Potential): A0QWG6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43883.49

構造登録者

Guerin, M.E.,Buschiazzo, A.,Kordulakova, J.,Jackson, M.,Alzari, P.M. (登録日: 2006-03-20, 公開日: 2007-04-03, 最終更新日: 2024-02-14)

主引用文献

Guerin, M.E.,Kordulakova, J.,Schaeffer, F.,Svetlikova, Z.,Buschiazzo, A.,Giganti, D.,Gicquel, B.,Mikusova, K.,Jackson, M.,Alzari, P.M.
Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria.
J.Biol.Chem., 282:20705-20714, 2007

PubMed Abstract: Mycobacterial phosphatidylinositol mannosides (PIMs) and metabolically derived cell wall lipoglycans play important roles in host-pathogen interactions, but their biosynthetic pathways are poorly understood. Here we focus on Mycobacterium smegmatis PimA, an essential enzyme responsible for the initial mannosylation of phosphatidylinositol. The structure of PimA in complex with GDP-mannose shows the two-domain organization and the catalytic machinery typical of GT-B glycosyltransferases. PimA is an amphitrophic enzyme that binds mono-disperse phosphatidylinositol, but its transferase activity is stimulated by high concentrations of non-substrate anionic surfactants, indicating that the early stages of PIM biosynthesis involve lipid-water interfacial catalysis. Based on structural, calorimetric, and mutagenesis studies, we propose a model wherein PimA attaches to the membrane through its N-terminal domain, and this association leads to enzyme activation. Our results reveal a novel mode of phosphatidylinositol recognition and provide a template for the development of potential antimycobacterial compounds.

PubMed: 17510062
DOI: 10.1074/jbc.M702087200

実験手法

X-RAY DIFFRACTION (2.4 Å)