4MTA

Crystal structure of Pim-1 kinase domain in complex with 2-methyl-5-phenylfuran-3-carboxylic acid

4MTA の概要

• エントリーDOI: 10.2210/pdb4mta/pdb
• 分子名称: Serine/threonine-protein kinase pim-1, 2-methyl-5-phenylfuran-3-carboxylic acid, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: serine/threonine-protein kinase, atp-binding, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33140.58

構造登録者

Scheufler, C.,Be, C. (登録日: 2013-09-19, 公開日: 2015-01-14, 最終更新日: 2023-09-20)

主引用文献

Kutchukian, P.S.,Wassermann, A.M.,Lindvall, M.K.,Wright, S.K.,Ottl, J.,Jacob, J.,Scheufler, C.,Marzinzik, A.,Brooijmans, N.,Glick, M.
Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.
J Biomol Screen, 20:588-596, 2015

PubMed Abstract: A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits.

PubMed: 25550355
DOI: 10.1177/1087057114565080

実験手法

X-RAY DIFFRACTION (2.2 Å)