%0 Journal Article %1 campbell2016crystal %A Campbell, J. C. %A VanSchouwen, B. %A Lorenz, R. %A Sankaran, B. %A Herberg, F. W. %A Melacini, G. %A Kim, C. %D 2017 %J FEBS Letters %K herberg myown %N 1 %P 221-230 %R 10.1002/1873-3468.12505 %T Crystal structure of cGMP-dependent protein kinase Iβ cyclic nucleotide-binding-B domain : Rp-cGMPS complex reveals an apo-like, inactive conformation %U http://dx.doi.org/10.1002/1873-3468.12505 %V 591 %X The R-enantiomer 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 Iβ cyclic nucleotide-binding domain (PKG Iβ CNB-B), considered a 'gatekeeper' for cGMP activation, bound to Rp-cGMPS at 1.3 Å. Our structural and NMR data show that PKG Iβ 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.This article is protected by copyright. All rights reserved.

@article{campbell2016crystal, abstract = {The R-enantiomer 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 Iβ cyclic nucleotide-binding domain (PKG Iβ CNB-B), considered a 'gatekeeper' for cGMP activation, bound to Rp-cGMPS at 1.3 Å. Our structural and NMR data show that PKG Iβ 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.This article is protected by copyright. All rights reserved.}, added-at = {2016-12-05T09:09:34.000+0100}, author = {Campbell, J. C. and VanSchouwen, B. and Lorenz, R. and Sankaran, B. and Herberg, F. W. and Melacini, G. and Kim, C.}, biburl = {https://www.bibsonomy.org/bibtex/2039b91dc0a2f2bc2b7de789a1c6af86f/biochemie}, description = {Crystal structure of PKG Iβ CNB-B:Rp-cGMPS complex reveals an apo-like, inactive conformation - Campbell - 2016 - FEBS Letters - Wiley Online Library}, doi = {10.1002/1873-3468.12505}, interhash = {54a55e71e02d11d7c0f6e0285549ee5e}, intrahash = {039b91dc0a2f2bc2b7de789a1c6af86f}, issn = {1873-3468}, journal = {FEBS Letters}, keywords = {herberg myown}, number = 1, pages = {221-230}, timestamp = {2017-05-02T15:14:14.000+0200}, title = {Crystal structure of cGMP-dependent protein kinase Iβ cyclic nucleotide-binding-B domain : Rp-cGMPS complex reveals an apo-like, inactive conformation}, url = {http://dx.doi.org/10.1002/1873-3468.12505}, volume = 591, year = 2017 }