| Structural highlights
1wax is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 1a5y, 1aax, 1bzc, 1bzh, 1bzj, 1c83, 1c84, 1c85, 1c86, 1c87, 1c88, 1ecv, 1een, 1eeo, 1g1f, 1g1g, 1g1h, 1g7f, 1g7g, 1gfy, 1i57, 1jf7, 1kak, 1kav, 1l8g, 1lqf, 1nl9, 1nny, 1no6, 1nwe, 1nwl, 1nz7, 1oem, 1oeo, 1oes, 1oet, 1oeu, 1oev, 1ony, 1onz, 1pa1, 1ph0, 1ptt, 1ptu, 1ptv, 1pty, 1pxh, 1pyn, 1q1m, 1q6j, 1q6m, 1q6n, 1q6p, 1q6s, 1q6t, 1qxk, 1sug, 1t48, 1t49, 1t4j, 1xbo, 2hnp, 2hnq |
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 |
| 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
Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper.
Fragment-based lead discovery using X-ray crystallography.,Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854[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
- ↑ Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H. Fragment-based lead discovery using X-ray crystallography. J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854 doi:http://dx.doi.org/10.1021/jm0495778
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