5QG4
PanDDA analysis group deposition -- Crystal structure of PTP1B in complex with compound_FMOOA000666a
Summary for 5QG4
| Entry DOI | 10.2210/pdb5qg4/pdb |
| Group deposition | PanDDA analysis group deposition of models with modelled events (e.g. bound ligands) (G_1002043) |
| Descriptor | Tyrosine-protein phosphatase non-receptor type 1, methyl (1S,3S,4R)-4-hydroxy-3-[(1S)-1-hydroxypropyl]-2-azabicyclo[2.2.2]octane-2-carboxylate, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total) |
| Functional Keywords | pandda, sgc - diamond i04-1 fragment screening, protein tyrosine phosphatase, ptp, protein tyrosine phosphatase 1b, ptp1b, enzyme, allostery, multiconformer, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37711.00 |
| Authors | Keedy, D.A.,Hill, Z.B.,Biel, J.T.,Kang, E.,Rettenmaier, T.J.,Brandao-Neto, J.,von Delft, F.,Wells, J.A.,Fraser, J.S. (deposition date: 2018-08-30, release date: 2018-10-10, Last modification date: 2024-11-13) |
| Primary citation | Keedy, D.A.,Hill, Z.B.,Biel, J.T.,Kang, E.,Rettenmaier, T.J.,Brandao-Neto, J.,Pearce, N.M.,von Delft, F.,Wells, J.A.,Fraser, J.S. An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering. Elife, 7:-, 2018 Cited by PubMed Abstract: 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. PubMed: 29877794DOI: 10.7554/eLife.36307 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.788 Å) |
Structure validation
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