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PDBsum entry 3zmp
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Hydrolase/peptide
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PDB id
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3zmp
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PDB id:
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| Name: |
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Hydrolase/peptide
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Title:
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Src-derived peptide inhibitor complex of ptp1b
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Structure:
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Tyrosine-protein phosphatase non-receptor type 1. Chain: a, b. Fragment: tyrosine-protein phosphatase domain, residues 1-321. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes. Mutation: yes. Proto-oncogene tyrosine-protein kinase src. Chain: c, d. Fragment: residues 527-536.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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2.62Å
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R-factor:
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0.223
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R-free:
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0.271
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Authors:
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K.Temmerman,V.Pogenberg,C.Meyer,M.Koehn,M.Wilmanns
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Key ref:
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C.Meyer
et al.
(2014).
Development of accessible peptidic tool compounds to study the phosphatase PTP1B in intact cells.
Acs Chem Biol,
9,
769-776.
PubMed id:
DOI:
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Date:
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12-Feb-13
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Release date:
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22-Jan-14
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PROCHECK
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Headers
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References
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P18031
(PTN1_HUMAN) -
Tyrosine-protein phosphatase non-receptor type 1 from Homo sapiens
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Seq:
Struc:
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435 a.a.
276 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.3.1.3.48
- protein-tyrosine-phosphatase.
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Reaction:
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O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
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O-phospho-L-tyrosyl-[protein]
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+
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H2O
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=
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L-tyrosyl-[protein]
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+
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phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Acs Chem Biol
9:769-776
(2014)
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PubMed id:
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Development of accessible peptidic tool compounds to study the phosphatase PTP1B in intact cells.
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C.Meyer,
B.Hoeger,
K.Temmerman,
M.Tatarek-Nossol,
V.Pogenberg,
J.Bernhagen,
M.Wilmanns,
A.Kapurniotu,
M.Köhn.
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ABSTRACT
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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.
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Links
