3ZMP

Src-derived peptide inhibitor complex of PTP1B

Summary for 3ZMP

• Entry DOI: 10.2210/pdb3zmp/pdb
• Descriptor: TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 1, PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC (3 entities in total)
• Functional Keywords: hydrolase-peptide complex, enzyme inhibitors, structure-activity relationship, transferase, hydrolase/peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031; Cell membrane: P12931
• Total number of polymer chains: 4
• Total formula weight: 79471.99

Authors

Temmerman, K.,Pogenberg, V.,Meyer, C.,Koehn, M.,Wilmanns, M. (deposition date: 2013-02-12, release date: 2014-01-22, Last modification date: 2023-12-20)

Primary citation

Meyer, C.,Hoeger, B.,Temmerman, K.,Tatarek-Nossol, M.,Pogenberg, V.,Bernhagen, J.,Wilmanns, M.,Kapurniotu, A.,Kohn, M.
Development of Accessible Peptidic Tool Compounds to Study the Phosphatase Ptp1B in Intact Cells.
Acs Chem.Biol., 9:769-, 2014

PubMed Abstract: Protein tyrosine phosphatases (PTPs) play crucial roles in health and disease. Chemical modulators of their activity are vital tools to study their function. An important aspect is the accessibility of these tools, which is usually limited or not existent due to the required, often complex synthesis of the molecules. We describe here a strategy for the development of cellular active inhibitors and in-cell detection tools for PTP1B as a model PTP, which plays important roles in diabetes, obesity, and cancer. The tool compounds are based on a peptide sequence from PTP1B's substrate Src, and the resulting compounds are commercially accessible through standard peptide synthesis. The peptide inhibitor is remarkably selective against a panel of PTPs. We provide the co-crystal structure of PTP1B with the sequence from Src and the optimized peptide inhibitor, showing the molecular basis of the interaction of PTP1B with part of its natural substrate and explaining the crucial interactions to enhance binding affinity, which are made possible by simple optimization of the sequence. Our approach enables the broad accessibility of PTP1B tools to researchers and has the potential for the systematic development of accessible PTP modulators to enable the study of PTPs.

PubMed: 24387659
DOI: 10.1021/CB400903U

Experimental method

X-RAY DIFFRACTION (2.619 Å)