STRUCTURAL BASIS FOR PHOSPHOTYROSINE PEPTIDE RECOGNITION BY PROTEIN-TYROSINE-PHOSPHATASE 1B
STRUCTURAL BASIS FOR PHOSPHOTYROSINE PEPTIDE RECOGNITION BY PROTEIN-TYROSINE-PHOSPHATASE 1B
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DOI：
10.1126/science.7540771
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发表时间：
1995-06-23
期刊：
影响因子：
56.9
通讯作者：
TONKS, NK
中科院分区：
文献类型：
--
作者：
JIA, ZC;BARFORD, D;TONKS, NK
蛋白酪氨酸磷酸酶1B的半胱氨酸-215-->丝氨酸突变体与对应于表皮生长因子受体的自磷酸化位点的高亲和力肽底物复合的晶体结构被确定。肽结合的蛋白磷酸酶伴随着一个表面环的构象变化，创造了一个磷酸酪氨酸识别口袋，并诱导催化活性形式的酶。磷酸酪氨酸侧链埋在蛋白质内，并将肽底物锚定在其结合位点。肽主链原子和蛋白质之间的氢键有助于结合亲和力，并且肽的酸性残基与酶表面上的碱性残基的特异性相互作用赋予序列特异性。
The crystal structures of a cysteine-215 --> serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosphatase was accompanied by a conformational change of a surface loop that created a phosphotyrosine recognition pocket and induced a catalytically competent form of the enzyme. The phosphotyrosine side chain is buried within the protein and anchors the peptide substrate to its binding site. Hydrogen bonds between peptide main-chain atoms and the protein contribute to binding affinity, and specific interactions of acidic residues of the peptide with basic residues on the surface of the enzyme confer sequence specificity.