4ZG9: Structural Basis For Inhibition Of Human Autotaxin By Four Novel Compounds

Citation:
Abstract
Autotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is a bioactive phospholipid that regulates diverse biological processes, including cell proliferation, migration, and survival/apoptosis, through the activation of a family of G protein-coupled receptors. The ATX-LPA pathway has been implicated in many pathologic conditions, including cancer, fibrosis, inflammation, cholestatic pruritus, and pain. Therefore, ATX inhibitors represent an attractive strategy for the development of therapeutics to treat a variety of diseases. Mouse and rat ATX have been crystallized previously with LPA or small-molecule inhibitors bound. Here, we present the crystal structures of human ATX in complex with four previously unpublished, structurally distinct ATX inhibitors. We demonstrate that the mechanism of inhibition of each compound reflects its unique interactions with human ATX. Our studies may provide a basis for the rational design of novel ATX inhibitors.
PDB ID: 4ZG9Download
MMDB ID: 133299
PDB Deposition Date: 2015/4/22
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 2.95  Å
Source Organism:
Similar Structures:
Biological Unit for 4ZG9: monomeric; determined by author
Molecular Components in 4ZG9
Label Count Molecule
Protein (1 molecule)
1
Ectonucleotide Pyrophosphatase/phosphodiesterase Family Member 2(Gene symbol: ENPP2)
Molecule annotation
Chemicals (11 molecules)
1
2
2
2
3
1
4
2
5
2
6
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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