PDBsum entry 5edg

Hydrolase

PDB id: 5edg

Contents

Protein chains

313 a.a.

Ligands

5MG ×4

Metals

_ZN ×4

_MG ×4

Waters ×319

PDB id:

5edg

Name:

Hydrolase

Title:

Crystal structure of human phosphodiesterase 10 in complex with c1(c(nc([nh]1)cl)c2ccccc2)c4=nn(c3cccc(c3)oc(f)(f)f)c=cc4=o, micromolar ic50=0.029618

Structure:

Camp and camp-inhibited cgmp 3',5'-cyclic phosphodiesterase 10a. Chain: a, c, d. Engineered: yes. Camp and camp-inhibited cgmp 3',5'-cyclic phosphodiesterase 10a. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pde10a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.30Å R-factor: 0.215 R-free: 0.261

Authors:

C.Joseph,M.G.Rudolph

Key ref:

B.Kuhn et al. (2016). A Real-World Perspective on Molecular Design. J Med Chem, 59, 4087-4102. PubMed id: 26878596 DOI: 10.1021/acs.jmedchem.5b01875

Date:

21-Oct-15 Release date: 09-Mar-16

Protein chains

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

Seq: 1055 a.a.

Struc: 313 a.a.*

* 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.
• Reaction: a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H⁺

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

Added reference

DOI no: 10.1021/acs.jmedchem.5b01875

J Med Chem 59:4087-4102 (2016)

PubMed id: 26878596

A Real-World Perspective on Molecular Design.

B.Kuhn, W.Guba, J.Hert, D.Banner, C.Bissantz, S.Ceccarelli, W.Haap, M.Körner, A.Kuglstatter, C.Lerner, P.Mattei, W.Neidhart, E.Pinard, M.G.Rudolph, T.Schulz-Gasch, T.Woltering, M.Stahl.

ABSTRACT

We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.