CAD protein

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Function

CAD protein is a trifunctional enzyme which contains dihydroorotase domain (DHO), aspartate transcarbamoylase domain (ATC) and carbamoylphosphate synthetase domain[1]. The CAD protein catalyzes the first 3 of 6 reactions required for pyrimidine biosynthesis.

Disease

Deficiency in carbamoylphosphate synthetase leads to lack of urea and hyperammonemia[2]

Relevance

Structural highlights

The 3D structure of CAD protein dihydroorotase subunit complex with dihydroorotate shows the containing and a flexible loop containing conserved Thr and Phe in a loop-out conformation[3]. Water molecules are shown as red spheres.

3D structures of CAD protein

CAD protein 3D structures

Human CAD protein dihydroorotatase subunit containing modified Lys complex with dihydroorotate, formate and Zn+2 ions (PDB ID 6hg3)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Moreno-Morcillo M, Grande-Garcia A, Ruiz-Ramos A, Del Cano-Ochoa F, Boskovic J, Ramon-Maiques S. Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis. Structure. 2017 Jun 6;25(6):912-923.e5. doi: 10.1016/j.str.2017.04.012. Epub 2017, May 25. PMID:28552578 doi:http://dx.doi.org/10.1016/j.str.2017.04.012
  2. Ng BG, Wolfe LA, Ichikawa M, Markello T, He M, Tifft CJ, Gahl WA, Freeze HH. Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors. Hum Mol Genet. 2015 Jun 1;24(11):3050-7. doi: 10.1093/hmg/ddv057. Epub 2015 Feb, 12. PMID:25678555 doi:http://dx.doi.org/10.1093/hmg/ddv057
  3. Del Cano-Ochoa F, Grande-Garcia A, Reverte-Lopez M, D'Abramo M, Ramon-Maiques S. Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD. J Biol Chem. 2018 Oct 12. pii: RA118.005494. doi: 10.1074/jbc.RA118.005494. PMID:30315107 doi:http://dx.doi.org/10.1074/jbc.RA118.005494

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