1PH0

Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site

1PH0 の概要

• エントリーDOI: 10.2210/pdb1ph0/pdb
• 関連するPDBエントリー: 1N06 1NL9 1NNY 1NZ7 1ONY 1ONZ
• 分子名称: Protein-tyrosine phosphatase, non-receptor type 1, 2-{4-[2-(S)-ALLYLOXYCARBONYLAMINO-3-{4-[(2-CARBOXY-PHENYL)-OXALYL-AMINO]-PHENYL}-PROPIONYLAMINO]-BUTOXY}-6-HYDROXY-BENZ OIC ACID METHYL ESTER (3 entities in total)
• 機能のキーワード: protein tyrosine phosphatase 1b, oxalyl-aryl-benzoic acid compound inhibitor, salicylic acid moiety at the second site, 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: 38043.29

構造登録者

Liu, G.,Xin, Z.,Liang, H.,Abad-Zapatero, C.,Hajduk, P.,Janowick, D.,Szczepankiewicz, B.,Pei, Z.,Hutchins, C.W.,Ballaron, S.J. (登録日: 2003-05-29, 公開日: 2003-07-29, 最終更新日: 2023-08-16)

主引用文献

Liu, G.,Xin, Z.,Liang, H.,Abad-Zapatero, C.,Hajduk, P.J.,Janowick, D.A.,Szczepankiewicz, B.G.,Pei, Z.,Hutchins, C.W.,Ballaron, S.J.,Stashko, M.A.,Lubben, T.H.,Berg, C.E.,Rondinone, C.M.,Trevillyan, J.M.,Jirousek, M.R.
Selective Protein Tyrosine Phosphatase 1B Inhibitors: Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands.
J.Med.Chem., 46:3437-3440, 2003

PubMed Abstract: Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling cascades. We identified several salicylic acid-based ligands for the second phosphotyrosine binding site of PTP1B using a NMR-based screening. Structure-based linking with a catalytic site-directed oxalylarylaminobenzoic acid-based pharmacophore led to the identification of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity over the highly homologous T-cell PTPase (TCPTP) and high selectivity over other phosphatases.

PubMed: 12877578
DOI: 10.1021/jm034088d

実験手法

X-RAY DIFFRACTION (2.2 Å)