1GFY

RESIDUE 259 IS A KEY DETERMINANT OF SUBSTRATE SPECIFICITY OF PROTEIN-TYROSINE PHOSPHATASE 1B AND ALPHA

1GFY の概要

• エントリーDOI: 10.2210/pdb1gfy/pdb
• 関連するPDBエントリー: 1C83 1C84 1C85 1C86 1C87 1C88 1ECV
• 分子名称: PROTEIN (PROTEIN-TYROSINE PHOSPHATASE 1B), 2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]THIOPYRAN-3-CARBOXYLIC ACID (3 entities in total)
• 機能のキーワード: 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: 34991.85

構造登録者

Iversen, L.F. (登録日: 2000-06-26, 公開日: 2000-07-04, 最終更新日: 2023-12-27)

主引用文献

Peters, G.H.,Iversen, L.F.,Branner, S.,Andersen, H.S.,Mortensen, S.B.,Olsen, O.H.,Moller, K.B.,Moller, N.P.
Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha.
J.Biol.Chem., 275:18201-18209, 2000

PubMed Abstract: The aim of this study was to define the structural elements that determine the differences in substrate recognition capacity of two protein-tyrosine phosphatases (PTPs), PTP1B and PTPalpha, both suggested to be negative regulators of insulin signaling. Since the Ac-DADE(pY)L-NH(2) peptide is well recognized by PTP1B, but less efficiently by PTPalpha, it was chosen as a tool for these analyses. Calpha regiovariation analyses and primary sequence alignments indicate that residues 47, 48, 258, and 259 (PTP1B numbering) define a selectivity-determining region. By analyzing a set of DADE(pY)L analogs with a series of PTP mutants in which these four residues were exchanged between PTP1B and PTPalpha, either in combination or alone, we here demonstrate that the key selectivity-determining residue is 259. In PTPalpha, this residue is a glutamine causing steric hindrance and in PTP1B a glycine allowing broad substrate recognition. Significantly, replacing Gln(259) with a glycine almost turns PTPalpha into a PTP1B-like enzyme. By using a novel set of PTP inhibitors and x-ray crystallography, we further provide evidence that Gln(259) in PTPalpha plays a dual role leading to restricted substrate recognition (directly via steric hindrance) and reduced catalytic activity (indirectly via Gln(262)). Both effects may indicate that PTPalpha regulates highly selective signal transduction processes.

PubMed: 10748206
DOI: 10.1074/jbc.M910273199

実験手法

X-RAY DIFFRACTION (2.13 Å)