Neutron Crystallography Detects Differences in Protein Dynamics: Structure of the PKG II Cyclic Nucleotide Binding Domain in Complex with an Activator.
Biochemistry
; 57(12): 1833-1837, 2018 03 27.
Article
em En
| MEDLINE
| ID: mdl-29517905
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 II8-pCPT-cGMP and previously reported PKG IßcGMP 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tionucleotídeos
/
GMP Cíclico
/
Ativadores de Enzimas
/
Proteína Quinase Dependente de GMP Cíclico Tipo II
Limite:
Humans
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos