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3sme

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Structure of PTP1B inactivated by H2O2/bicarbonate

Structural highlights

3sme 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 1.7Å
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]

Publication Abstract from PubMed

Hydrogen peroxide is a cell signaling agent that inactivates protein tyrosine phosphatases (PTPs) via oxidation of their catalytic cysteine residue. PTPs are inactivated rapidly during H(2)O(2)-mediated cellular signal transduction processes, but, paradoxically, hydrogen peroxide is a rather sluggish PTP inactivator in vitro. Here we present evidence that the biological buffer bicarbonate/CO(2) potentiates the ability of H(2)O(2) to inactivate PTPs. The results of biochemical experiments and high-resolution crystallographic analysis are consistent with a mechanism involving oxidation of the catalytic cysteine residue by peroxymonocarbonate generated via the reaction of H(2)O(2) with HCO(3)(-)/CO(2).

The Biological Buffer Bicarbonate/CO(2) Potentiates H(2)O(2)-Mediated Inactivation of Protein Tyrosine Phosphatases.,Zhou H, Singh H, Parsons ZD, Lewis SM, Bhattacharya S, Seiner DR, Labutti JN, Reilly TJ, Tanner JJ, Gates KS J Am Chem Soc. 2011 Oct 12;133(40):15803-5. Epub 2011 Sep 19. PMID:21913686^[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
↑ Zhou H, Singh H, Parsons ZD, Lewis SM, Bhattacharya S, Seiner DR, Labutti JN, Reilly TJ, Tanner JJ, Gates KS. The Biological Buffer Bicarbonate/CO(2) Potentiates H(2)O(2)-Mediated Inactivation of Protein Tyrosine Phosphatases. J Am Chem Soc. 2011 Oct 12;133(40):15803-5. Epub 2011 Sep 19. PMID:21913686 doi:10.1021/ja2077137