5O2S
Human KRAS in complex with darpin K27
Summary for 5O2S
| Entry DOI | 10.2210/pdb5o2s/pdb |
| Descriptor | GTPase KRas, darpin K27, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | kras, ras signalling, darpin, nucleotide exchange, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Cell membrane ; Lipid-anchor ; Cytoplasmic side : P01116 |
| Total number of polymer chains | 8 |
| Total formula weight | 156828.29 |
| Authors | Debreczeni, J.E.,Guillard, S.,Kolasinska-Zwierz, P.,Breed, J.,Zhang, J.,Bery, N.,Marwood, R.,Tart, J.,Stocki, P.,Mistry, B.,Phillips, C.,Rabbitts, T.,Jackson, R.,Minter, R. (deposition date: 2017-05-22, release date: 2017-07-26, Last modification date: 2024-05-08) |
| Primary citation | Guillard, S.,Kolasinska-Zwierz, P.,Debreczeni, J.,Breed, J.,Zhang, J.,Bery, N.,Marwood, R.,Tart, J.,Overman, R.,Stocki, P.,Mistry, B.,Phillips, C.,Rabbitts, T.,Jackson, R.,Minter, R. Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange. Nat Commun, 8:16111-16111, 2017 Cited by PubMed Abstract: Ras mutations are the oncogenic drivers of many human cancers and yet there are still no approved Ras-targeted cancer therapies. Inhibition of Ras nucleotide exchange is a promising new approach but better understanding of this mechanism of action is needed. Here we describe an antibody mimetic, DARPin K27, which inhibits nucleotide exchange of Ras. K27 binds preferentially to the inactive Ras GDP form with a K of 4 nM and structural studies support its selectivity for inactive Ras. Intracellular expression of K27 significantly reduces the amount of active Ras, inhibits downstream signalling, in particular the levels of phosphorylated ERK, and slows the growth in soft agar of HCT116 cells. K27 is a potent, non-covalent inhibitor of nucleotide exchange, showing consistent effects across different isoforms of Ras, including wild-type and oncogenic mutant forms. PubMed: 28706291DOI: 10.1038/ncomms16111 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.22 Å) |
Structure validation
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