PDBsum entry 5c6c

Protein binding

PDB id: 5c6c

Contents

Protein chains

119 a.a.

Ligands

CMP ×2

EDO

Metals

_NA

_CD ×6

_CO ×4

_CA ×2

Waters ×106

References listed in PDB file

Key reference

• Title: Structural basis of cyclic nucleotide selectivity in cgmp-Dependent protein kinase ii.
• Authors: J.C.Campbell, J.J.Kim, K.Y.Li, G.Y.Huang, A.S.Reger, S.Matsuda, B.Sankaran, T.M.Link, K.Yuasa, J.E.Ladbury, D.E.Casteel, C.Kim.
• Ref.: J Biol Chem, 2016, 291, 5623-5633. [DOI no: 10.1074/jbc.M115.691303]
• PubMed id: 26769964

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.