PDBsum entry 3wi2

Hydrolase/hydrolase inhibitor

PDB id

3wi2

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Contents

			Protein chains

					324 a.a.

			Ligands

					P98 ×2

			Metals

					_ZN ×2


					_MG ×2

			Waters ×13

PDB id:

3wi2

Links

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of pde10a in complex with inhibitor

Structure:

Camp and camp-inhibited cgmp 3',5'-cyclic phosphodiesterase 10a. Chain: a, b. Fragment: catalytic domain, unp residues 439-779. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pde10a. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.26Å

R-factor:

0.257

R-free:

0.329

Authors:

Y.Amano

Key ref:

W.Hamaguchi et al. (2013). Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition. Bioorg Med Chem Lett, 21, 7612-7623. PubMed id: 24238902 DOI: 10.1016/j.bmc.2013.10.035

Date:

04-Sep-13

Release date:

11-Dec-13

PROCHECK

	Headers

	References

Protein chains

Q9Y233 (PDE10_HUMAN) - cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:					1055 a.a. 324 a.a.*

Key:

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.3.1.4.17 - 3',5'-cyclic-nucleotide phosphodiesterase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H⁺

nucleoside 3',5'-cyclic phosphate	+	H2O	=	nucleoside 5'-phosphate	+	H(+)

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

Added reference

DOI no: 10.1016/j.bmc.2013.10.035	Bioorg Med Chem Lett 21:7612-7623 (2013)
PubMed id: 24238902

Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition.
W.Hamaguchi, N.Masuda, M.Isomura, S.Miyamoto, S.Kikuchi, Y.Amano, K.Honbou, T.Mihara, T.Watanabe.

ABSTRACT

A novel class of phosphodiesterase 10A (PDE10A) inhibitors with reduced CYP1A2 inhibition were designed and synthesized starting from 2-{[(1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (1). Introduction of an isopropyl group at the 2-position and a methoxy group at the 5-position of the benzimidazole ring of lead compound 1 resulted in the identification of 2-{[(2-isopropyl-5-methoxy-1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (25b), which exhibited potent PDE10A inhibitory activity with reduced CYP1A2 inhibitory activity compared to compound 1.