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3VBT

Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design

3VBT の概要
エントリーDOI10.2210/pdb3vbt/pdb
関連するPDBエントリー3VBQ 3VBV 3VBW 3VBX 3VBY 3VC4
分子名称Serine/threonine-protein kinase pim-1, 4-chloro-2-(1H-pyrazol-3-yl)phenol (3 entities in total)
機能のキーワードpim1, transferase-transferase inhibitor complex, transferase/transferase inhibitor
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34675.71
構造登録者
Liu, J. (登録日: 2012-01-02, 公開日: 2012-03-21, 最終更新日: 2024-02-28)
主引用文献Good, A.C.,Liu, J.,Hirth, B.,Asmussen, G.,Xiang, Y.,Biemann, H.P.,Bishop, K.A.,Fremgen, T.,Fitzgerald, M.,Gladysheva, T.,Jain, A.,Jancsics, K.,Metz, M.,Papoulis, A.,Skerlj, R.,Stepp, J.D.,Wei, R.R.
Implications of promiscuous Pim-1 kinase fragment inhibitor hydrophobic interactions for fragment-based drug design.
J.Med.Chem., 55:2641-2648, 2012
Cited by
PubMed Abstract: We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.
PubMed: 22339127
DOI: 10.1021/jm2014698
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2.23 Å)
構造検証レポート
Validation report summary of 3vbt
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-11-06に公開中

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