3S3H

Crystal structure of the catalytic domain of PTP10D from Drosophila melanogaster with a phosphopeptide substrate GP4

3S3H の概要

• エントリーDOI: 10.2210/pdb3s3h/pdb
• 分子名称: Tyrosine-protein phosphatase 10D, phosphopeptide GP4, 1-BUTANOL, ... (5 entities in total)
• 機能のキーワード: differentiation, neurogenesis, signal transduction, developmental protein, hydrolase, protein phosphatase, protein tyrosine phosphatase
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P35992
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 73480.00

構造登録者

Madan, L.L.,Gopal, B. (登録日: 2011-05-18, 公開日: 2011-11-02, 最終更新日: 2024-10-16)

主引用文献

Madan, L.L.,Gopal, B.
Conformational basis for substrate recruitment in protein tyrosine phosphatase 10D
Biochemistry, 50:10114-10125, 2011

PubMed Abstract: The coordinated activity of protein tyrosine phosphatases (PTPs) is crucial for the initiation, modulation, and termination of diverse cellular processes. The catalytic activity of this protein depends on a nucleophilic cysteine at the active site that mediates the hydrolysis of the incoming phosphotyrosine substrate. While the role of conserved residues in the catalytic mechanism of PTPs has been extensively examined, the diversity in the mechanisms of substrate recognition and modulation of catalytic activity suggests that other, less conserved sequence and structural features could contribute to this process. Here we describe the crystal structures of Drosophila melanogaster PTP10D in the apo form as well as in a complex with a substrate peptide and an inhibitor. These studies reveal the role of aromatic ring stacking interactions at the boundary of the active site of PTPs in mediating substrate recruitment. We note that phenylalanine 76, of the so-called KNRY loop, is crucial for orienting the phosphotyrosine residue toward the nucleophilic cysteine. Mutation of phenylalanine 76 to leucine results in a 60-fold decrease in the catalytic efficiency of the enzyme. Fluorescence measurements with a competitive inhibitor, p-nitrocatechol sulfate, suggest that Phe76 also influences the formation of the enzyme-substrate intermediate. The structural and biochemical data for PTP10D thus highlight the role of relatively less conserved residues in PTP domains in both substrate recruitment and modulation of reaction kinetics.

PubMed: 22007620
DOI: 10.1021/bi201092q

実験手法

X-RAY DIFFRACTION (2.8 Å)