5bv6

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

spinqualitylabelsall models 5bv6, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5bv6 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 35G, ACT, CA, NA Activity: Transferase, with EC number 2.7.11.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed 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, compared to 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 D412 and R415 of the alphaC-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. Structural Basis of Cyclic Nucleotide Selectivity in cGMP-Dependent Protein Kinase II.,Campbell JC, Kim JJ, Li KY, Huang GY, Reger AS, Matsuda S, Sankaran B, Link TM, Yuasa K, Ladbury JE, Casteel DE, Kim C J Biol Chem. 2016 Jan 14. pii: jbc.M115.691303. PMID:26769964 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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