2QBP

Crystal structure of ptp1b-inhibitor complex

2QBP の概要

• エントリーDOI: 10.2210/pdb2qbp/pdb
• 関連するPDBエントリー: 2AZR 2HB1 2QBQ 2QBR 2QBS
• 分子名称: Tyrosine-protein phosphatase non-receptor type 1, 5-(3-{[1-(BENZYLSULFONYL)PIPERIDIN-4-YL]AMINO}PHENYL)-4-BROMO-3-(CARBOXYMETHOXY)THIOPHENE-2-CARBOXYLIC ACID (3 entities in total)
• 機能のキーワード: protein-inhibitor complex, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35443.23

構造登録者

Xu, W. (登録日: 2007-06-18, 公開日: 2008-03-18, 最終更新日: 2024-02-21)

主引用文献

Wilson, D.P.,Wan, Z.K.,Xu, W.X.,Kirincich, S.J.,Follows, B.C.,Joseph-McCarthy, D.,Foreman, K.,Moretto, A.,Wu, J.,Zhu, M.,Binnun, E.,Zhang, Y.L.,Tam, M.,Erbe, D.V.,Tobin, J.,Xu, X.,Leung, L.,Shilling, A.,Tam, S.Y.,Mansour, T.S.,Lee, J.
Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site.
J.Med.Chem., 50:4681-4698, 2007

PubMed Abstract: Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enzyme active site into the second phosphotyrosine binding site is described. Medicinal chemistry, guided by X-ray complex structure and molecular modeling, has yielded low nanomolar PTP1B inhibitors in an efficient manner. Compounds from this chemical series were found to be actively transported into hepatocytes. This active uptake into target tissues could be one of the possible avenues to overcome the poor membrane permeability of PTP1B inhibitors.

PubMed: 17705360
DOI: 10.1021/jm0702478

実験手法

X-RAY DIFFRACTION (2.5 Å)