PDBsum entry 4qx5

Transferase

PDB id: 4qx5

Contents

Protein chain

127 a.a.

Ligands

CMP

Metals

IOD ×18

Waters ×119

PDB id:

4qx5

Name:

Transferase

Title:

Neutron diffraction reveals hydrogen bonds critical for cgmp-selective activation: insights for pkg agonist design

Structure:

Cgmp-dependent protein kinase 1. Chain: a. Fragment: c-terminal cgmp-binding domain. Synonym: cgk 1, 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: 562.

Resolution:

1.32Å R-factor: 0.203 R-free: 0.224

Authors:

G.Y.Huang,O.O.Gerlits,M.P.Blakeley,B.Sankaran,A.Y.Kovalevsky,C.Kim

Key ref:

G.Y.Huang et al. (2014). Neutron diffraction reveals hydrogen bonds critical for cGMP-selective activation: insights for cGMP-dependent protein kinase agonist design. Biochemistry, 53, 6725-6727. PubMed id: 25271401 DOI: 10.1021/bi501012v

Date:

18-Jul-14 Release date: 12-Nov-14

Protein chain

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

Seq: 671 a.a.

Struc: 127 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] (Bound ligand (Het Group name = CMP) matches with 81.48% similarity) + ADP + H(+)

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

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

reference

DOI no: 10.1021/bi501012v

Biochemistry 53:6725-6727 (2014)

PubMed id: 25271401

Neutron diffraction reveals hydrogen bonds critical for cGMP-selective activation: insights for cGMP-dependent protein kinase agonist design.

G.Y.Huang, O.O.Gerlits, M.P.Blakeley, B.Sankaran, A.Y.Kovalevsky, C.Kim.

ABSTRACT

High selectivity of cyclic-nucleotide binding (CNB) domains for cAMP and cGMP are required for segregating signaling pathways; however, the mechanism of selectivity remains unclear. To investigate the mechanism of high selectivity in cGMP-dependent protein kinase (PKG), we determined a room-temperature joint X-ray/neutron (XN) structure of PKG Iβ CNB-B, a domain 200-fold selective for cGMP over cAMP, bound to cGMP (2.2 Å), and a low-temperature X-ray structure of CNB-B with cAMP (1.3 Å). The XN structure directly describes the hydrogen bonding interactions that modulate high selectivity for cGMP, while the structure with cAMP reveals that all these contacts are disrupted, explaining its low affinity for cAMP.