Crystal structure of cGMP-dependent protein kinase Iß cyclic nucleotide-binding-B domain : Rp-cGMPS complex reveals an apo-like, inactive conformation.
FEBS Lett
; 591(1): 221-230, 2017 Jan.
Article
in En
| MEDLINE
| ID: mdl-27914169
ABSTRACT
The R-diastereomer of phosphorothioate analogs of cGMP, Rp-cGMPS, is one of few known inhibitors of cGMP-dependent protein kinase I (PKG I); however, its mechanism of inhibition is currently not fully understood. Here, we determined the crystal structure of the PKG Iß cyclic nucleotide-binding domain (PKG Iß CNB-B), considered a 'gatekeeper' for cGMP activation, bound to Rp-cGMPS at 1.3 Å. Our structural and NMR data show that PKG Iß CNB-B bound to Rp-cGMPS displays an apo-like structure with its helical domain in an open conformation. Comparison with the cAMP-dependent protein kinase regulatory subunit (PKA RIα) showed that this conformation resembles the catalytic subunit-bound inhibited state of PKA RIα more closely than the apo or Rp-cAMPS-bound conformations. These results suggest that Rp-cGMPS inhibits PKG I by stabilizing the inactive conformation of CNB-B.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thionucleotides
/
Apoenzymes
/
Cyclic GMP
/
Cyclic GMP-Dependent Protein Kinase Type I
Language:
En
Journal:
FEBS Lett
Year:
2017
Type:
Article
Affiliation country:
United States