PDBsum entry 4z07

Transferase

PDB id: 4z07

Contents

Protein chains

260 a.a.

126 a.a.

Ligands

PCG ×5

SO4

IPA ×2

Waters ×330

PDB id:

4z07

Name:

Transferase

Title:

Co-crystal structure of the tandem cnb (cnb-a/b) domains of human pkg i beta with cgmp

Structure:

Cgmp-dependent protein kinase 1. Chain: a, c, e. Fragment: unp residues 92-351. Synonym: cgk1,cgmp-dependent protein kinase i,cgki. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prkg1, prkg1b, prkgr1a, prkgr1b. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.50Å R-factor: 0.165 R-free: 0.224

Authors:

J.J.Kim,A.S.Reger,S.T.Arold,C.Kim

Key ref:

J.J.Kim et al. (2016). Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation. Structure, 24, 710-720. PubMed id: 27066748

Date:

25-Mar-15 Release date: 13-Apr-16

Protein chains

Q13976  (KGP1_HUMAN) -  cGMP-dependent protein kinase 1 from Homo sapiens

Seq: 671 a.a.

Struc: 260 a.a.*

Protein chain

Q13976  (KGP1_HUMAN) -  cGMP-dependent protein kinase 1 from Homo sapiens

Seq: 671 a.a.

Struc: 126 a.a.*

* PDB and UniProt seqs differ at 22 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, C, E: 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] (Bound ligand (Het Group name = PCG) matches with 78.57% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = PCG) matches with 78.57% similarity) + ADP + H(+)

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

reference

Structure 24:710-720 (2016)

PubMed id: 27066748

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation.

J.J.Kim, R.Lorenz, S.T.Arold, A.S.Reger, B.Sankaran, D.E.Casteel, F.W.Herberg, C.Kim.

ABSTRACT

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG.