5C8W

PKG II's Amino Terminal Cyclic Nucleotide Binding Domain (CNB-A) in a complex with cGMP

Summary for 5C8W

• Entry DOI: 10.2210/pdb5c8w/pdb
• Descriptor: cGMP-dependent protein kinase 2, MALONIC ACID, CYCLIC GUANOSINE MONOPHOSPHATE, ... (5 entities in total)
• Functional Keywords: binding sites, cyclic amp, cyclic gmp, cyclic gmp-dependent protein kinase type ii, mutagenesis, site-directed, protein binding, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Apical cell membrane ; Lipid-anchor : Q13237
• Total number of polymer chains: 6
• Total formula weight: 102330.27

Authors

Campbell, J.C.,Reger, A.S.,Huang, G.Y.,Sankaran, B.,Kim, J.J.,Kim, C.W. (deposition date: 2015-06-26, release date: 2016-01-20, Last modification date: 2024-03-06)

Primary citation

Campbell, J.C.,Kim, J.J.,Li, K.Y.,Huang, G.Y.,Reger, A.S.,Matsuda, S.,Sankaran, B.,Link, T.M.,Yuasa, K.,Ladbury, J.E.,Casteel, D.E.,Kim, C.
Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II.
J.Biol.Chem., 291:5623-5633, 2016

PubMed Abstract: Membrane-bound cGMP-dependent protein kinase (PKG) II is a key regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKG II binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine-specific contacts at Asp-412 and Arg-415 of the αC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II.

PubMed: 26769964
DOI: 10.1074/jbc.M115.691303

Experimental method

X-RAY DIFFRACTION (1.8 Å)