6b90 | pdb_00006b90

Multiconformer model of apo WT PTP1B with glycerol at 100 K (ALTERNATIVE REFINEMENT OF PDB 1SUG showing conformational heterogeneity)

spinqualitylabelsall models 6b90, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6b90 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 1.95Å Ligands: GOL, TRS 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. Publication Abstract from PubMed Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function. An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.,Keedy DA, Hill ZB, Biel JT, Kang E, Rettenmaier TJ, Brandao-Neto J, Pearce NM, von Delft F, Wells JA, Fraser JS Elife. 2018 Jun 7;7. pii: 36307. doi: 10.7554/eLife.36307. PMID:29877794 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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