The Asn674Ile CPS1 variant is in the bicarbonate phosphorylation region & converts a polar uncharged amino acid to one that is nonpolar and hydrophobic. (A) The domain composition is noted and the amino acid location is identified by the numerals. The mutation is in the C-terminal moiety with bicarbonate phosphorylation, the first 2 steps in the production of carbamoyl phosphate by phosphorylation of bicarbonate by ATP to produce carboxyphosphate followed by attack by NH3 to yield carbamate. (B) Cartoon representation and enlargement (inset) of the ligand-bound human CPS1 protein transparency set to 50%. Asn674 is highlighted in red sticks. ADP in the bicarbonate phosphorylation domain is shown in red, orange, yellow and blue sticks. K+ and Mg2+ ions are shown in purple and green spheres, respectively. Catalytic residues around ADP are shown in light green lines. The yellow dashed line indicates the distance between the center of the Asn674 residue and the center of ADP in angstroms.
Stuti Bakshi & co develop a hypomorphic mouse model of carbamoyl phosphate synthetase 1 deficiency, allowing for the assessment of the effects of mild hyperammonemia on development, with potential applications in new therapeutic advancements. 🐭
doi.org/10.1242/dmm....
#Hyperammonemia
