3UIB

Map kinase LMAMPK10 from leishmania major in complex with SB203580

3UIB の概要

• エントリーDOI: 10.2210/pdb3uib/pdb
• 関連するPDBエントリー: 3PG1
• 分子名称: mitogen-activated protein kinase, 4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE (3 entities in total)
• 機能のキーワード: eukariotic protein kinase fold, transferase
• 由来する生物種: Leishmania major
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41836.81

構造登録者

Horjales, S.,Schmidt-Arras, D.,Leclercq, O.,Spath, G.,Buschiazzo, A. (登録日: 2011-11-04, 公開日: 2012-09-19, 最終更新日: 2024-02-28)

主引用文献

Horjales, S.,Schmidt-Arras, D.,Limardo, R.R.,Leclercq, O.,Obal, G.,Prina, E.,Turjanski, A.G.,Spath, G.F.,Buschiazzo, A.
The Crystal Structure of the MAP Kinase LmaMPK10 from Leishmania Major Reveals Parasite-Specific Features and Regulatory Mechanisms.
Structure, 20:1649-1660, 2012

PubMed Abstract: Mitogen-activated protein kinases (MAPKs) are involved in environmental signal sensing. They are thus expected to play key roles in the biology of Trypanosomatid parasites, which display complex life cycles and use extracellular cues to modulate cell differentiation. Despite their relevance, structural data of Trypanosomatid MAPKs is lacking. We have now determined the crystal structure of Leishmania major LmaMPK10, a stage-specifically activated MAPK, both alone and in complex with SB203580. LmaMPK10 was observed to be more similar to p38 than to other human MAPKs. However, significant differences could be identified in the catalytic pocket, as well as in potentially regulatory sites in the N-terminal lobe. The modified pocket architecture in LmaMPK10 precludes DFG-in/DFG-out regulatory flipping as observed in mammalian MAPKs. LmaMPK10-nucleotide association was also studied, revealing a potential C-terminal autoinhibitory mechanism. Overall, these data should speed the discovery of molecules interfering with LmaMPK10 functions, with relevance for antileishmanial drug development strategies.

PubMed: 22884419
DOI: 10.1016/j.str.2012.07.005

実験手法

X-RAY DIFFRACTION (2.65 Å)