9EEY

STEP (PTPN5) with active-site disulfide bond and allosteric-site loop shift

9EEY の概要

• エントリーDOI: 10.2210/pdb9eey/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 5, SULFATE ION (3 entities in total)
• 機能のキーワード: step, ptpn5, allostery, disulfide, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35396.97

構造登録者

Guerrero, L.,Ebrahim, A.,Riley, B.T.,Keedy, D.A. (登録日: 2024-11-19, 公開日: 2024-12-11, 最終更新日: 2026-02-04)

主引用文献

Guerrero, L.,Ebrahim, A.,Riley, B.T.,Kim, S.H.,Bishop, A.C.,Wu, J.,Han, Y.N.,Tautz, L.,Keedy, D.A.
Three STEPs Forward: A Trio of Unexpected Structures of PTPN5.
Proteins, 93:2112-2127, 2025

PubMed Abstract: Protein tyrosine phosphatases (PTPs) play pivotal roles in myriad cellular processes by counteracting protein tyrosine kinases. Striatal-enriched protein tyrosine phosphatase (STEP, PTPN5) regulates synaptic function and neuronal plasticity in the brain and is a therapeutic target for several neurological disorders. Here, we present three new crystal structures of STEP, each with unexpected features. These include high-resolution conformational heterogeneity at multiple sites, a highly coordinated citrate molecule in the active site, a previously unseen conformational change at an allosteric site, an intramolecular disulfide bond that was characterized biochemically but had never been visualized structurally, and two serendipitous covalent ligand binding events at surface-exposed cysteines that are nearly or entirely unique to STEP among human PTPs. Together, our results offer new views of the conformational landscape of STEP that may inform structure-based design of allosteric small molecules to specifically inhibit this biomedically important enzyme.

PubMed: 40616465
DOI: 10.1002/prot.70013

実験手法

X-RAY DIFFRACTION (1.75 Å)