Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition.

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作者：

Mauro Sarmiento,§,‖，Yoram A. Puius,§,‖，Stefan W. Vetter,§,⊥，YenFang Keng,⊥，Li Wu,⊥，Yu Zhao,⊥，David S. Lawrence,§，Steven C. Almo,,§ and，ZhongYin Zhang,§,⊥

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摘要：

Protein tyrosine phosphatase 1B (PTP1B) displays a preference for peptides containing acidic as well as aromatic/aliphatic residues immediately NH2-terminal to phosphotyrosine. The structure of PTP1B bound with DADEpYL-NH2 (EGFR988-993) offers a structural explanation for PTP1B's preference for acidic residues [Jia, Z., Barford, D., Flint, A. J., and Tonks, N. K. (1995) Science 268, 1754−1758]. We report here the crystal structures of PTP1B in complex with Ac-ELEFpYMDYE-NH2 (PTP1B·Con) and Ac-DAD(Bpa)pYLIPQQG (PTP1B·Bpa) determined to 1.8 and 1.9 Å resolution, respectively. A structural analysis of PTP1B·Con and PTP1B·Bpa shows how aromatic/aliphatic residues at the −1 and −3 positions of peptide substrates are accommodated by PTP1B. A comparison of the structures of PTP1B·Con and PTP1B·Bpa with that of PTP1B·EGFR988-993 reveals the structural basis for the plasticity of PTP1B substrate recognition. PTP1B is able to bind phosphopeptides by utilizing common interactions involving the aromatic ring and phos...

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关键词：

Arginine Peptides Enzyme Inhibitors Protein Conformation Substrate Specificity Kinetics Protein Tyrosine Phosphatases Protein Tyrosine Phosphatase, Non-Receptor Type 1 Crystallization Models, Molecular