3ZM4

Crystal structure of MEK1 in complex with fragment 1

Summary for 3ZM4

• Entry DOI: 10.2210/pdb3zm4/pdb
• Related: 3ZLS 3ZLW 3ZLX 3ZLY
• Descriptor: DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1, 7-chloranyl-6-[(3S)-pyrrolidin-3-yl]oxy-2H-isoquinolin-1-one (3 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 39181.59

Authors

Amaning, K.,Lowinsky, M.,Vallee, F.,Steier, V.,Marcireau, C.,Ugolini, A.,Delorme, C.,McCort, G.,Andouche, C.,Vougier, S.,Llopart, S.,Halland, N.,Rak, A. (deposition date: 2013-02-05, release date: 2013-05-22, Last modification date: 2024-05-08)

Primary citation

Amaning, K.,Lowinski, M.,Vallee, F.,Steier, V.,Marcireau, C.,Ugolini, A.,Delorme, C.,Foucalt, F.,Mccort, G.,Derimay, N.,Andouche, C.,Vougier, S.,Llopart, S.,Halland, N.,Rak, A.
The Use of Virtual Screening and Differential Scanning Fluorimetry for the Rapid Identification of Fragments Active Against Mek1.
Bioorg.Med.Chem.Lett., 23:3620-, 2013

PubMed Abstract: We report the analysis of an in-house fragment screening campaign for the oncology target MEK1. The application of virtual screening (VS) as a primary fragment screening approach, followed by biophysical validation using differential screening fluorimetry (DSF), with resultant binding mode determination by X-ray crystallography (X-ray), is presented as the most time and cost-effective combination of in silico and in vitro methods to identify fragments. We demonstrate the effectiveness of the VS-DSF workflow for the early identification of fragments to both 'jump-start' the drug discovery project and to complement biochemical screening data.

PubMed: 23648182
DOI: 10.1016/J.BMCL.2013.04.003

Experimental method

X-RAY DIFFRACTION (2.37 Å)