Final Coordinates and Maps for Positive Datasets from a Fragment Screening Campaign Targeting Human DHODH

Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme in the de novo pyrimidine biosynthesis pathway, catalyzing the conversion of dihydroorotate to orotate. This process is essential for the synthesis of uridine triphosphate (UTP) and other pyrimidine nucleotides, which are critical for DNA and RNA production. As such, HsDHODH is a prominent therapeutic target for addressing proliferative, viral, and parasitic diseases.

This dataset originates from a crystallographic fragment screening campaign aimed at identifying novel binding sites on HsDHODH using the 96 fragment F2X-Entry Library. The study revealed six distinct binding regions, including the canonical ubiquinone binding site, which accommodates all class 2 DHODH inhibitors, as well as additional novel sites.

The dataset includes final files from crystal structures with fragments bound to the protein:

PDB files containing final coordinates for ensemble models of bound and unbound states.

MTZ files containing structure factors and phases used to generate conventional maps, as well as structure factors from PanDDA event maps and Z-maps.

These data provide structural information into the molecular interactions of HsDHODH with fragments.