Dihydroorotase Domain of Human CAD

DHO is a zinc-dependent enzyme that catalyzes the third step of the pathway for de novo biosynthesis of pyrimidine nucleotides, the reversible cyclization of N-carbamoyl-l-aspartate (CA-asp) to dihydroorotate (CA-asp2− + H+ dihydroorotate− + H2O). In animals, DHO is integrated into CAD, a multienzymatic complex catalyzing the first three steps of the de novo pyrimidine pathway. CAD is a 1.5 MDa homohexamer formed by the self-association of a 243 kDa polypeptide composed of four contiguous functional domains: glutaminase (GLN), carbamoyl phosphate synthetase (CPS; EC 6.3.5.5), aspartate transcarbamoylase (ATC; EC 2.1.3.2), and DHO. 3D Structure Cartoon representation of the structure of the DHO domain of human CAD. Human DHO forms dimers and each subunit is shown in a different color. Three Zn2+ ions bound per protein subunit are represented as cyan spheres. PDB code: 4C6C. Dashed lines indicate the linkers connecting the N- and C-termini of DHO to the CPS and ATC domains, respectively. The structure representations are produced with program PyMOL (The PyMOL Molecular Graphics System, Schrodinger, LLC). Keywords: CAD; pyrimidine nucleotides; carbamoyl phosphate synthetase; aspartate transcarbamoylase

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