Crystal structures of human ENPP1 in apo and bound forms. Issue 9 (2nd September 2020)

• Record Type: Journal Article
• Authors: Dennis, Matthew L.; Newman, Janet; Dolezal, Olan; Hattarki, Meghan; Surjadi, Regina N.; Nuttall, Stewart D.; Pham, Tam; Nebl, Tom; Camerino, Michelle; Khoo, Poh Sim; Monahan, Brendon J.; Peat, Thomas S.
• Is Part Of: Acta crystallographica. Volume 76:Issue 9(2020)
• Page Start: 889
• Page End: 898
• Publication Date: 2020-09-02
• Subjects: cancer -- inhibitor structures -- pyrophosphatase/phosphodiesterases -- ENPP1; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798320010505
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : Structures of the cancer target human ENPP1 have been determined in the apo form, bound to nucleotides and bound to known inhibitors of the enzyme. 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.