5UK9

Wild-type K-Ras(GCP) pH 6.5

Summary for 5UK9

• Entry DOI: 10.2210/pdb5uk9/pdb
• Related: 5UKC 5UKS 5UKU
• Descriptor: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: gtpase, k-ras, ras, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 39057.87

Authors

Parker, J.A.,Mattos, C. (deposition date: 2017-01-20, release date: 2018-01-10, Last modification date: 2023-10-04)

Primary citation

Parker, J.A.,Volmar, A.Y.,Pavlopoulos, S.,Mattos, C.
K-Ras Populates Conformational States Differently from Its Isoform H-Ras and Oncogenic Mutant K-RasG12D.
Structure, 26:810-, 2018

PubMed Abstract: Structures of wild-type K-Ras from crystals obtained in the presence of guanosine triphosphate (GTP) or its analogs have remained elusive. Of the K-Ras mutants, only K-RasG12D and K-RasQ61H are available in the PDB representing the activated form of the GTPase not in complex with other proteins. We present the crystal structure of wild-type K-Ras bound to the GTP analog GppCHp, with K-Ras in the state 1 conformation. Signatures of conformational states obtained by one-dimensional proton NMR confirm that K-Ras has a more substantial population of state 1 in solution than H-Ras, which predominantly favors state 2. The oncogenic mutant K-RasG12D favors state 2, changing the balance of conformational states in favor of interactions with effector proteins. Differences in the population of conformational states between K-Ras and H-Ras, as well as between K-Ras and its mutants, can provide a structural basis for focused targeting of the K-Ras isoform in cancer-specific strategies.

PubMed: 29706533
DOI: 10.1016/j.str.2018.03.018

Experimental method

X-RAY DIFFRACTION (1.887 Å)