6BQ8
Joint X-ray/neutron structure of PKG II CNB-B domain in complex with 8-pCPT-cGMP
Summary for 6BQ8
| Entry DOI | 10.2210/pdb6bq8/pdb |
| Descriptor | cGMP-dependent protein kinase 2, 2-(~2~H_2_)amino-8-[(4-chlorophenyl)sulfanyl]-9-[(2S,4aR,6R,7R,7aS)-2-hydroxy-7-(~2~H)hydroxy-2-oxotetrahydro-2H,4H-2lambda~5~-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl](~2~H)-1,9-dihydro-6H-purin-6-one, STRONTIUM ION, ... (5 entities in total) |
| Functional Keywords | protein kinase g, regulatory domain, neutron crystallography, activator, hydrogen bonding, protonation state, signaling protein, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 18087.98 |
| Authors | Kim, C.,Kovalevsky, A.,Gerlits, O. (deposition date: 2017-11-27, release date: 2018-03-21, Last modification date: 2024-04-03) |
| Primary citation | Gerlits, O.,Campbell, J.C.,Blakeley, M.P.,Kim, C.,Kovalevsky, A. Neutron Crystallography Detects Differences in Protein Dynamics: Structure of the PKG II Cyclic Nucleotide Binding Domain in Complex with an Activator. Biochemistry, 57:1833-1837, 2018 Cited by PubMed Abstract: As one of the main receptors of a second messenger, cGMP, cGMP-dependent protein kinase (PKG) isoforms I and II regulate distinct physiological processes. The design of isoform-specific activators is thus of great biomedical importance and requires detailed structural information about PKG isoforms bound with activators, including accurate positions of hydrogen atoms and a description of the hydrogen bonding and water architecture. Here, we determined a 2.2 Å room-temperature joint X-ray/neutron (XN) structure of the human PKG II carboxyl cyclic nucleotide binding (CNB-B) domain bound with a potent PKG II activator, 8-pCPT-cGMP. The XN structure directly visualizes intermolecular interactions and reveals changes in hydrogen bonding patterns upon comparison to the X-ray structure determined at cryo-temperatures. Comparative analysis of the backbone hydrogen/deuterium exchange patterns in PKG II:8-pCPT-cGMP and previously reported PKG Iβ:cGMP XN structures suggests that the ability of these agonists to activate PKG is related to how effectively they quench dynamics of the cyclic nucleotide binding pocket and the surrounding regions. PubMed: 29517905DOI: 10.1021/acs.biochem.8b00010 PDB entries with the same primary citation |
| Experimental method | NEUTRON DIFFRACTION (2.2 Å) X-RAY DIFFRACTION (2 Å) |
Structure validation
Download full validation report
