PDBsum entry 3hmv

Hydrolase

PDB id: 3hmv

Contents

Protein chains

351 a.a. *

Ligands

HBT ×2

GOL

Metals

_ZN ×2

_MG ×2

Waters ×255

* Residue conservation analysis

PDB id:

3hmv

Name:

Hydrolase

Title:

Catalytic domain of human phosphodiesterase 4b2b in complex with a tetrahydrobenzothiophene inhibitor

Structure:

Camp-specific 3',5'-cyclic phosphodiesterase 4b. Chain: a, b. Fragment: catalytic domain, unp residues 324-700. Synonym: dpde4, pde32. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pde4b, dpde4. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.23Å R-factor: 0.176 R-free: 0.226

Authors:

D.O.Somers,M.Neu

Key ref:

M.Kranz et al. (2009). Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode. Bioorg Med Chem Lett, 17, 5336-5341. PubMed id: 19525117

Date:

29-May-09 Release date: 09-Jun-10

Protein chains

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

Seq: 736 a.a.

Struc: 351 a.a.*

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

Enzyme reactions

• Enzyme class: 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 17:5336-5341 (2009)

PubMed id: 19525117

Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode.

M.Kranz, M.Wall, B.Evans, A.Miah, S.Ballantine, C.Delves, B.Dombroski, J.Gross, J.Schneck, J.P.Villa, M.Neu, D.O.Somers.

ABSTRACT

A PDE4B over 4D-selective inhibitor programme was initiated to capitalise on the recently discovered predominance of the PDE4B subtype in inflammatory cell regulation. The SAR of a tetrahydrobenzothiophene (THBT) series did not agree with either of two proposed docking modes in the 4B binding site. A subsequent X-ray co-crystal structure determination revealed that the THBT ligand displaces the Gln-443 residue, invariably ligand-anchoring in previous PDE4 co-crystal structures, and even shifts helix-15 by 1-2A. For the first time, several residues of the C-terminus previously proposed to be involved in subtype selectivity are resolved and three of them extend into the ligand binding site potentially allowing for selective drug design.