3RS0

H-Ras soaked in neat cyclopentanol: one of 10 in MSCS set

3RS0 の概要

• エントリーDOI: 10.2210/pdb3rs0/pdb
• 関連するPDBエントリー: 3RRY 3RRZ 3RS2 3RS3 3RS4 3RS5 3RS7 3RSL 3RSO
• 分子名称: GTPase HRas, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, cyclopentanol, ... (6 entities in total)
• 機能のキーワード: gtp-binding, nucleotide binding, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane. Isoform 2: Nucleus: P01112
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19698.42

構造登録者

Mattos, C.,Buhrman, G.,Kearney, B. (登録日: 2011-05-02, 公開日: 2011-09-21, 最終更新日: 2024-02-28)

主引用文献

Buhrman, G.,O Connor, C.,Zerbe, B.,Kearney, B.M.,Napoleon, R.,Kovrigina, E.A.,Vajda, S.,Kozakov, D.,Kovrigin, E.L.,Mattos, C.
Analysis of Binding Site Hot Spots on the Surface of Ras GTPase.
J.Mol.Biol., 413:773-789, 2011

PubMed Abstract: We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the "off" and "on" allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.

PubMed: 21945529
DOI: 10.1016/j.jmb.2011.09.011

実験手法

X-RAY DIFFRACTION (1.4 Å)