2XYN

HUMAN ABL2 IN COMPLEX WITH AURORA KINASE INHIBITOR VX-680

「3NSV」から置き換えられました

2XYN の概要

• エントリーDOI: 10.2210/pdb2xyn/pdb
• 分子名称: TYROSINE-PROTEIN KINASE ABL2, SODIUM ION, CYCLOPROPANECARBOXYLIC ACID {4-[4-(4-METHYL-PIPERAZIN-1-YL)-6-(5-METHYL-2H-PYRAZOL-3-YLAMINO)-PYRIMIDIN-2-YLSULFANYL]-PHENYL}-AMIDE, ... (5 entities in total)
• 機能のキーワード: cell adhesion, structural genomics consortium, sgc, transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 103963.61

構造登録者

Salah, E.,Ugochukwu, E.,Elkins, J.M.,Barr, A.J.,Shrestha, B.,Savitsky, P.,Mahajan, P.,Muniz, J.R.C.,Yue, W.W.,Chaikuad, A.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2010-11-18, 公開日: 2010-12-01, 最終更新日: 2023-12-20)

主引用文献

Salah, E.,Ugochukwu, E.,Barr, A.J.,von Delft, F.,Knapp, S.,Elkins, J.M.
Crystal Structures of Abl-Related Gene (Abl2) in Complex with Imatinib, Tozasertib (Vx-680), and a Type I Inhibitor of the Triazole Carbothioamide Class.
J.Med.Chem., 54:2359-, 2011

PubMed Abstract: ABL2 (also known as ARG (ABL related gene)) is closely related to the well-studied Abelson kinase cABL. ABL2 is involved in human neoplastic diseases and is deregulated in solid tumors. Oncogenic gene translocations occur in acute leukemia. So far no structural information for ABL2 has been reported. To elucidate structural determinants for inhibitor interaction, we determined the cocrystal structure of ABL2 with the oncology drug imatinib. Interestingly, imatinib not only interacted with the ATP binding site of the inactive kinase but was also bound to the regulatory myristate binding site. This structure may therefore serve as a tool for the development of allosteric ABL inhibitors. In addition, we determined the structures of ABL2 in complex with VX-680 and with an ATP-mimetic type I inhibitor, which revealed an interesting position of the DFG motif intermediate between active and inactive conformations, that may also serve as a template for future inhibitor design.

PubMed: 21417343
DOI: 10.1021/JM101506N

実験手法

X-RAY DIFFRACTION (2.81 Å)