PDBsum entry 3jsi

Hydrolase

PDB id

3jsi

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Contents

			Protein chain

					328 a.a. *

			Ligands

					WTC ×2

			Metals

					_ZN ×2


					_MG ×2

			Waters ×29

* Residue conservation analysis

PDB id:

3jsi

Links

Name:

Hydrolase

Title:

Human phosphodiesterase 9 in complex with inhibitor

Structure:

High affinity cgmp-specific 3',5'-cyclic phosphodiesterase 9a. Chain: a, b. Fragment: catalytic domain: unp residues 242-566. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pde9a. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.72Å

R-factor:

0.205

R-free:

0.218

Authors:

S.Liu

Key ref:

P.R.Verhoest et al. (2009). Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy. J Med Chem, 52, 7946-7949. PubMed id: 19919087

Date:

10-Sep-09

Release date:

01-Dec-09

PROCHECK

	Headers

	References

Protein chains

O76083 (PDE9A_HUMAN) - High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A from Homo sapiens

Seq: Struc:

Seq: Struc:					593 a.a. 328 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 4 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.3.1.4.35 - 3',5'-cyclic-GMP phosphodiesterase.

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

Reaction:

3',5'-cyclic GMP + H2O = GMP + H⁺

3',5'-cyclic GMP
Bound ligand (Het Group name = WTC)
matches with 40.62% similarity

H2O

GMP

H(+)

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

Added reference

	J Med Chem 52:7946-7949 (2009)
PubMed id: 19919087

Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy.
P.R.Verhoest, C.Proulx-Lafrance, M.Corman, L.Chenard, C.J.Helal, X.Hou, R.Kleiman, S.Liu, E.Marr, F.S.Menniti, C.J.Schmidt, M.Vanase-Frawley, A.W.Schmidt, R.D.Williams, F.R.Nelson, K.R.Fonseca, S.Liras.

ABSTRACT

By use of chemical enablement and prospective design, a novel series of selective, brain penetrant PDE9A inhibitors have been identified that are capable of producing in vivo elevations of brain cGMP.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20976216

C.Giampà, D.Laurenti, S.Anzilotti, G.Bernardi, F.S.Menniti, and F.R.Fusco (2010).
Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

PLoS One, 5, e13417.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.