6WEW

Crystal structures of human E-NPP 1: bound to N-{4-[(7-methoxyquinolin-4-yl)oxy]phenyl}sulfuric diamide

This is a non-PDB format compatible entry.

Summary for 6WEW

• Entry DOI: 10.2210/pdb6wew/pdb
• Descriptor: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, 1,2-ETHANEDIOL, beta-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: human e-npp 1; drug discovery; inhibitors, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 215035.33

Authors

Peat, T.S.,Dennis, M.,Newman, J. (deposition date: 2020-04-03, release date: 2020-09-09, Last modification date: 2023-10-18)

Primary citation

Dennis, M.L.,Newman, J.,Dolezal, O.,Hattarki, M.,Surjadi, R.N.,Nuttall, S.D.,Pham, T.,Nebl, T.,Camerino, M.,Khoo, P.S.,Monahan, B.J.,Peat, T.S.
Crystal structures of human ENPP1 in apo and bound forms.
Acta Crystallogr D Struct Biol, 76:889-898, 2020

PubMed Abstract: Cancer is one of the leading causes of mortality in humans, and recent work has focused on the area of immuno-oncology, in which the immune system is used to specifically target cancerous cells. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an emerging therapeutic target in human cancers owing to its role in degrading cyclic GMP-AMP (cGAMP), an agonist of the stimulator of interferon genes (STING). The available structures of ENPP1 are of the mouse enzyme, and no structures are available with anything other than native nucleotides. Here, the first X-ray crystal structures of the human ENPP1 enzyme in an apo form, with bound nucleotides and with two known inhibitors are presented. The availability of these structures and a robust crystallization system will allow the development of structure-based drug-design campaigns against this attractive cancer therapeutic target.

PubMed: 32876064
DOI: 10.1107/S2059798320010505

Experimental method

X-RAY DIFFRACTION (2.73 Å)