3SLS

Crystal Structure of human MEK-1 kinase in complex with UCB1353770 and AMPPNP

3SLS の概要

• エントリーDOI: 10.2210/pdb3sls/pdb
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: serine-threonine kinase, signalling, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, centrosome: Q02750
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69960.33

構造登録者

Meier, C.,Ceska, T.A. (登録日: 2011-06-25, 公開日: 2012-02-29, 最終更新日: 2024-02-28)

主引用文献

Meier, C.,Brookings, D.C.,Ceska, T.A.,Doyle, C.,Gong, H.,McMillan, D.,Saville, G.P.,Mushtaq, A.,Knight, D.,Reich, S.,Pearl, L.H.,Powell, K.A.,Savva, R.,Allen, R.A.
Engineering human MEK-1 for structural studies: A case study of combinatorial domain hunting.
J.Struct.Biol., 177:329-334, 2012

PubMed Abstract: Structural biology studies typically require large quantities of pure, soluble protein. Currently the most widely-used method for obtaining such protein involves the use of bioinformatics and experimental methods to design constructs of the target, which are cloned and expressed. Recently an alternative approach has emerged, which involves random fragmentation of the gene of interest and screening for well-expressing fragments. Here we describe the application of one such fragmentation method, combinatorial domain hunting (CDH), to a target which historically was difficult to express, human MEK-1. We show how CDH was used to identify a fragment which covers the kinase domain of MEK-1 and which expresses and crystallizes significantly better than designed expression constructs, and we report the crystal structure of this fragment which explains some of its superior properties. Gene fragmentation methods, such as CDH, thus hold great promise for tackling difficult-to-express target proteins.

PubMed: 22245778
DOI: 10.1016/j.jsb.2012.01.002

実験手法

X-RAY DIFFRACTION (2.3 Å)