4Q02

Second-site screening of K-Ras in the presence of covalently attached first-site ligands

4Q02 の概要

• エントリーDOI: 10.2210/pdb4q02/pdb
• 関連するPDBエントリー: 4PZY 4PZZ 4Q01 4Q03
• 分子名称: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: small gtpase, signaling transduction, sos, raf, cytosol, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side: P01116
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19984.56

構造登録者

Sun, Q.,Phan, J.,Friberg, A.,Camper, D.V.,Olejniczak, E.T.,Fesik, S.W. (登録日: 2014-03-31, 公開日: 2014-09-10)

主引用文献

Sun, Q.,Phan, J.,Friberg, A.R.,Camper, D.V.,Olejniczak, E.T.,Fesik, S.W.
A method for the second-site screening of K-Ras in the presence of a covalently attached first-site ligand.
J.Biomol.Nmr, 60:11-14, 2014

PubMed Abstract: K-Ras is a well-validated cancer target but is considered to be "undruggable" due to the lack of suitable binding pockets. We previously discovered small molecules that bind weakly to K-Ras but wanted to improve their binding affinities by identifying ligands that bind near our initial hits that we could link together. Here we describe an approach for identifying second site ligands that uses a cysteine residue to covalently attach a compound for tight binding to the first site pocket followed by a fragment screen for binding to a second site. This approach could be very useful for targeting Ras and other challenging drug targets.

PubMed: 25087006
DOI: 10.1007/s10858-014-9849-8

実験手法

X-RAY DIFFRACTION (1.702 Å)