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

PDB id:

5c6c

Name:

Protein binding

Title:

Pkg ii's amino terminal cyclic nucleotide binding domain (cnb-a) in a complex with camp

Structure:

Cgmp-dependent protein kinase 2. Chain: a, b. Fragment: unp residues 137-277. Synonym: cgk2,cgmp-dependent protein kinase ii,cgkii. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prkg2, prkgr2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.05Å R-factor: 0.192 R-free: 0.243

Authors:

J.C.Campbell,A.S.Reger,G.Y.Huang,B.Sankaran,J.J.Kim,C.W.Kim

Key ref:

J.C.Campbell et al. (2016). Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II. J Biol Chem, 291, 5623-5633. PubMed id: 26769964 DOI: 10.1074/jbc.M115.691303

Date:

22-Jun-15 Release date: 20-Jan-16

Protein chains

Q13237  (KGP2_HUMAN) -  cGMP-dependent protein kinase 2 from Homo sapiens

Seq: 762 a.a.

Struc: 119 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.12 - cGMP-dependent protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP (Bound ligand (Het Group name = CMP) matches with 81.48% similarity) + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP (Bound ligand (Het Group name = CMP) matches with 81.48% similarity) + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M115.691303

J Biol Chem 291:5623-5633 (2016)

PubMed id: 26769964

Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II.

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.

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.