6XY7
Human SHIP1 with magnesium and phosphate bound to the active site
This is a non-PDB format compatible entry.
Summary for 6XY7
| Entry DOI | 10.2210/pdb6xy7/pdb |
| Descriptor | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1, MAGNESIUM ION, PHOSPHATE ION, ... (6 entities in total) |
| Functional Keywords | phosphatidylinositol, phosphate, phosphatase, alzheimer's disease, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 53381.42 |
| Authors | Bradshaw, W.J.,Scacioc, A.,Fernandez-Cid, A.,Mckinley, G.,Burgess-Brown, N.A.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Gileadi, O. (deposition date: 2020-01-29, release date: 2020-02-26, Last modification date: 2024-02-14) |
| Primary citation | Bradshaw, W.J.,Kennedy, E.C.,Moreira, T.,Smith, L.A.,Chalk, R.,Katis, V.L.,Benesch, J.L.P.,Brennan, P.E.,Murphy, E.J.,Gileadi, O. Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2. Structure, 2024 Cited by PubMed Abstract: SHIP1, an inositol 5-phosphatase, plays a central role in cellular signaling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and magnesium and phosphate-bound structures of the phosphatase and C2 domains of SHIP1. The C2 domains of SHIP1 and the related SHIP2 modulate the activity of the phosphatase domain. To understand the mechanism, we performed activity assays, hydrogen-deuterium exchange mass spectrometry, and molecular dynamics on SHIP1 and SHIP2. Our findings demonstrate that the influence of the C2 domain is more pronounced for SHIP2 than SHIP1. We determined 91 structures of SHIP1 with fragments bound, with some near the interface between the two domains. We performed a mass spectrometry screen and determined four structures with covalent fragments. These structures could act as starting points for the development of potent, selective probes. PubMed: 38309262DOI: 10.1016/j.str.2024.01.005 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.086 Å) |
Structure validation
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