5NNL

Inactive dihydroorotase-like domain of Chaetomium thermophilum CAD-like multifunctional protein

Summary for 5NNL

• Entry DOI: 10.2210/pdb5nnl/pdb
• Descriptor: Inactive dihydroorotase-like domain (2 entities in total)
• Functional Keywords: tim-barrel, de novo pyrimidine biosynthesis, cad, ura2, oxidoreductase
• Biological source: Chaetomium thermophilum
• Total number of polymer chains: 2
• Total formula weight: 74755.59

Authors

Ramon-Maiques, S.,Moreno-Morcillo, M.,Grande-Garcia, A. (deposition date: 2017-04-10, release date: 2017-06-07, Last modification date: 2024-11-13)

Primary citation

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, 25:912-923.e5, 2017

PubMed Abstract: CAD, the multifunctional protein initiating and controlling de novo biosynthesis of pyrimidines in animals, self-assembles into ∼1.5 MDa hexamers. The structures of the dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains of human CAD have been previously determined, but we lack information on how these domains associate and interact with the rest of CAD forming a multienzymatic unit. Here, we prove that a construct covering human DHO and ATC oligomerizes as a dimer of trimers and that this arrangement is conserved in CAD-like from fungi, which holds an inactive DHO-like domain. The crystal structures of the ATC trimer and DHO-like dimer from the fungus Chaetomium thermophilum confirm the similarity with the human CAD homologs. These results demonstrate that, despite being inactive, the fungal DHO-like domain has a conserved structural function. We propose a model that sets the DHO and ATC complex as the central element in the architecture of CAD.

PubMed: 28552578
DOI: 10.1016/j.str.2017.04.012

Experimental method

X-RAY DIFFRACTION (2.13 Å)