PDBsum entry 3ly2

Hydrolase/hydrolase inhibitor

PDB id: 3ly2

Contents

Protein chains

345 a.a. *

328 a.a. *

Ligands

Z72 ×8

SO4 ×2

Metals

_MG ×8

_ZN ×8

Waters ×494

* Residue conservation analysis

PDB id:

3ly2

Name:

Hydrolase/hydrolase inhibitor

Title:

Catalytic domain of human phosphodiesterase 4b in complex with a coumarin-based inhibitor

Structure:

Camp-specific 3',5'-cyclic phosphodiesterase 4b. Chain: a, b, c, d, e, f, g, h. Fragment: catalytic domain, residues 324-659. Synonym: dpde4, pde32. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dpde4, pde4b. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.205 R-free: 0.233

Authors:

A.K.Shiau,A.R.Coyle,J.H.Hsien,L.M.Staszewski

Key ref:

S.P.Govek et al. (2010). Water-soluble PDE4 inhibitors for the treatment of dry eye. Bioorg Med Chem Lett, 20, 2928-2932. PubMed id: 20378348

Date:

26-Feb-10 Release date: 28-Apr-10

Protein chains

Q07343  (PDE4B_HUMAN) -  cAMP-specific 3',5'-cyclic phosphodiesterase 4B from Homo sapiens

Seq: 736 a.a.

Struc: 345 a.a.*

Protein chains

Q07343  (PDE4B_HUMAN) -  cAMP-specific 3',5'-cyclic phosphodiesterase 4B from Homo sapiens

Seq: 736 a.a.

Struc: 328 a.a.

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.3.1.4.53 - 3',5'-cyclic-AMP phosphodiesterase.
• Reaction: 3',5'-cyclic AMP + H2O = AMP + H⁺

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

Added reference

Bioorg Med Chem Lett 20:2928-2932 (2010)

PubMed id: 20378348

Water-soluble PDE4 inhibitors for the treatment of dry eye.

S.P.Govek, G.Oshiro, J.V.Anzola, C.Beauregard, J.Chen, A.R.Coyle, D.A.Gamache, M.R.Hellberg, J.N.Hsien, J.M.Lerch, J.C.Liao, J.W.Malecha, L.M.Staszewski, D.J.Thomas, J.M.Yanni, S.A.Noble, A.K.Shiau.

ABSTRACT

PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.