Neutron diffraction reveals hydrogen bonds critical for cGMP-selective activation: insights for cGMP-dependent protein kinase agonist design.
Biochemistry
; 53(43): 6725-7, 2014 Nov 04.
Article
in En
| MEDLINE
| ID: mdl-25271401
ABSTRACT
High selectivity of cyclic-nucleotide binding (CNB) domains for cAMP and cGMP are required for segregating signaling pathways; however, the mechanism of selectivity remains unclear. To investigate the mechanism of high selectivity in cGMP-dependent protein kinase (PKG), we determined a room-temperature joint X-ray/neutron (XN) structure of PKG Iß CNB-B, a domain 200-fold selective for cGMP over cAMP, bound to cGMP (2.2 Å), and a low-temperature X-ray structure of CNB-B with cAMP (1.3 Å). The XN structure directly describes the hydrogen bonding interactions that modulate high selectivity for cGMP, while the structure with cAMP reveals that all these contacts are disrupted, explaining its low affinity for cAMP.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Scattering, Radiation
/
Enzyme Activators
/
Cyclic GMP-Dependent Protein Kinase Type I
/
Neutrons
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochemistry
Year:
2014
Type:
Article
Affiliation country:
United States