4qx5

Publication Abstract from PubMed

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 Ibeta CNB-B, a domain 200-fold selective for cGMP over cAMP, bound to cGMP (2.2 A), and a low-temperature X-ray structure of CNB-B with cAMP (1.3 A). 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.

Neutron Diffraction Reveals Hydrogen Bonds Critical for cGMP-Selective Activation: Insights for cGMP-Dependent Protein Kinase Agonist Design.,Huang GY, Gerlits OO, Blakeley MP, Sankaran B, Kovalevsky AY, Kim C Biochemistry. 2014 Nov 4;53(43):6725-7. doi: 10.1021/bi501012v. Epub 2014 Oct 22. PMID:25271401^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.