Download MendeleyNeutron Diffraction Reveals Hydrogen Bonds Critical for cGMP-Selective Activation: Insights for cGMP-Dependent Protein Kinase Agonist Design.
Huang, G.Y., Gerlits, O.O., Blakeley, M.P., Sankaran, B., Kovalevsky, A.Y., Kim, C.(2014) Biochemistry 53: 6725-6727
- PubMed: 25271401
- DOI: https://doi.org/10.1021/bi501012v
- Primary Citation of Related Structures:
4QX5, 4QXK - PubMed 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 Iβ 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.
Organizational Affiliation:
Verna and Mars McClean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , One Baylor Plaza, Houston, Texas 77004, United States.
