1NWE

Ptp1B R47C Modified at C47 with N-[4-(2-{2-[3-(2-Bromo-acetylamino)-propionylamino]-3-hydroxy-propionylamino}-ethyl)-phenyl]-oxalamic acid

1NWE の概要

• エントリーDOI: 10.2210/pdb1nwe/pdb
• 分子名称: Protein-tyrosine phosphatase, non-receptor type 1, N-[4-(2-{2-[3-(2-BROMO-ACETYLAMINO)-PROPIONYLAMINO]-3-HYDROXY-PROPIONYLAMINO}-ETHYL)-PHENYL]-OXALAMIC ACID (2 entities in total)
• 機能のキーワード: hydrolase, acetylation, phosphorylation, phospatase, phosphotyrosine mimetic
• 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: 35133.74

構造登録者

Erlanson, D.A.,McDowell, R.S.,He, M.M.,Randal, M.,Simmons, R.L.,Kung, J.,Waight, A.,Hansen, S.K. (登録日: 2003-02-06, 公開日: 2003-05-06, 最終更新日: 2024-10-30)

主引用文献

Erlanson, D.A.,McDowell, R.S.,He, M.M.,Randal, M.,Simmons, R.L.,Kung, J.,Waight, A.,Hansen, S.K.
Discovery of a New Phosphotyrosine Mimetic for PTP1B Using Breakaway Tethering
J.Am.Chem.Soc., 125:5602-5603, 2003

PubMed Abstract: Protein tyrosine phosphatases play important roles in many signaling cascades involved in human disease. The identification of druglike inhibitors for these targets is a major challenge, and the discovery of suitable phosphotyrosine (pY) mimetics remains one of the key difficulties. Here we describe an extension of tethering technology, "breakaway tethering", which is ideally suited for discovering such new chemical entities. The approach involves first irreversibly modifying a protein with an extender that contains both a masked thiol and a known pY mimetic. The extender is then cleaved to release the pY mimetic, unmasking the thiol. The resulting protein is screened against a library of disulfide-containing small molecule fragments; any molecules with inherent affinity for the pY binding site will preferentially form disulfides with the extender, allowing for their identification by mass spectrometry. The ability to start from a known substrate mimimizes perturbation of protein structure and increases the opportunity to probe the active site using tethering. We applied this approach to the anti-diabetic protein PTP1B to discover a pY mimetic which belongs to a new molecular class and which binds in a novel fashion.

PubMed: 12733877
DOI: 10.1021/ja034440c

実験手法

X-RAY DIFFRACTION (3.1 Å)