PDBsum entry 4oex

Hydrolase/hydrolase inhibitor

PDB id: 4oex

Contents

Protein chain

297 a.a.

Ligands

5EO

Metals

_MG

_ZN

Waters ×164

PDB id:

4oex

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of the pde5a1 catalytic domain in complex with novel inhibitors

Structure:

Cgmp-specific 3',5'-cyclic phosphodiesterase. Chain: a. Fragment: unp residues 535-860. Synonym: cgmp-binding cgmp-specific phosphodiesterase, cgb-pde. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pde5, pde5a. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.14Å R-factor: 0.193 R-free: 0.240

Authors:

T.T.Chen,J.Ren,Y.C.Xu

Key ref:

J.Ren et al. (2014). Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors. J Med Chem, 57, 3588-3593. PubMed id: 24702184 DOI: 10.1021/jm5002315

Date:

14-Jan-14 Release date: 01-Apr-15

Supersedes:

3tse

Protein chain

O76074  (PDE5A_HUMAN) -  cGMP-specific 3',5'-cyclic phosphodiesterase from Homo sapiens

Seq: 875 a.a.

Struc: 297 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.4.35 - 3',5'-cyclic-GMP phosphodiesterase.
• Reaction: 3',5'-cyclic GMP + H2O = GMP + H⁺

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

Added reference

DOI no: 10.1021/jm5002315

J Med Chem 57:3588-3593 (2014)

PubMed id: 24702184

Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors.

J.Ren, Y.He, W.Chen, T.Chen, G.Wang, Z.Wang, Z.Xu, X.Luo, W.Zhu, H.Jiang, J.Shen, Y.Xu.

ABSTRACT

The significance of halogen bonding in protein-ligand interactions has been recognized recently. We present here the first comprehensive thermodynamic and structural characterization of halogen bonding in PDE5-inhibitor interactions. ITC studies reveal that binding strength of the halogen bonding between chlorine, bromine, and iodine of inhibitor and the protein is -1.57, -3.09, and -5.59 kJ/mol, respectively. The halogens interact with the designed residue Y612 and an unexpected buried water molecule.