2bgd

Structure-based design of Protein Tyrosine Phosphatase-1B InhibitorsStructure-based design of Protein Tyrosine Phosphatase-1B Inhibitors

Structural highlights

2bgd 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 2.4Å
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

Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template.

Structure-based design of protein tyrosine phosphatase-1B inhibitors.,Black E, Breed J, Breeze AL, Embrey K, Garcia R, Gero TW, Godfrey L, Kenny PW, Morley AD, Minshull CA, Pannifer AD, Read J, Rees A, Russell DJ, Toader D, Tucker J Bioorg Med Chem Lett. 2005 May 16;15(10):2503-7. PMID:15863305^[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
↑ Black E, Breed J, Breeze AL, Embrey K, Garcia R, Gero TW, Godfrey L, Kenny PW, Morley AD, Minshull CA, Pannifer AD, Read J, Rees A, Russell DJ, Toader D, Tucker J. Structure-based design of protein tyrosine phosphatase-1B inhibitors. Bioorg Med Chem Lett. 2005 May 16;15(10):2503-7. PMID:15863305 doi:http://dx.doi.org/10.1016/j.bmcl.2005.03.068

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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] Black E, Breed J, Breeze AL, Embrey K, Garcia R, Gero TW, Godfrey L, Kenny PW, Morley AD, Minshull CA, Pannifer AD, Read J, Rees A, Russell DJ, Toader D, Tucker J. Structure-based design of protein tyrosine phosphatase-1B inhibitors. Bioorg Med Chem Lett. 2005 May 16;15(10):2503-7. PMID:15863305 doi:http://dx.doi.org/10.1016/j.bmcl.2005.03.068

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