1pyn

DUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR USING A LINKED FRAGMENT STRATEGY AND A MALONATE HEAD ON THE FIRST SITEDUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR USING A LINKED FRAGMENT STRATEGY AND A MALONATE HEAD ON THE FIRST SITE

Structural highlights

1pyn is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTN1_HUMAN Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A salicylate second site binder was linked to three classes of phosphotyrosine mimetics to produce potent protein tyrosine phosphatase 1B (PTP1B) inhibitors which exhibit significant selectivity against other phosphatases including the most homologous member, TCPTP.

Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors.,Pei Z, Li X, Liu G, Abad-Zapatero C, Lubben T, Zhang T, Ballaron SJ, Hutchins CW, Trevillyan JM, Jirousek MR Bioorg Med Chem Lett. 2003 Oct 6;13(19):3129-32. PMID:12951078^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035
↑ Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329
↑ Pei Z, Li X, Liu G, Abad-Zapatero C, Lubben T, Zhang T, Ballaron SJ, Hutchins CW, Trevillyan JM, Jirousek MR. Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3129-32. PMID:12951078

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OCA

[1] Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035

[2] Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329

[3] Pei Z, Li X, Liu G, Abad-Zapatero C, Lubben T, Zhang T, Ballaron SJ, Hutchins CW, Trevillyan JM, Jirousek MR. Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3129-32. PMID:12951078

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