RGD Reference Report - Required allosteric effector site for N-acetylglutamate on carbamoyl-phosphate synthetase I. - Rat Genome Database

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Required allosteric effector site for N-acetylglutamate on carbamoyl-phosphate synthetase I.

Authors: McCudden, CR  Powers-Lee, SG 
Citation: McCudden CR and Powers-Lee SG, J Biol Chem. 1996 Jul 26;271(30):18285-94.
RGD ID: 4144107
Pubmed: PMID:8663466   (View Abstract at PubMed)

Carbamoyl-phosphate synthetase I (CPSase I) catalyzes the entry and rate-limiting step in the urea cycle, the pathway by which mammals detoxify ammonia. One facet of CPSase I regulation is a requirement for N-acetylglutamate (AGA), which induces an active enzyme conformation and does not participate directly in the chemical reaction. We have utilized labeling with carbodiimide-activated [14C]AGA to identify peptides 120-127, 234-237, 625-630, and 1351-1356 as potentially being near the binding site for AGA. Identification of peptide 1351-1356 confirms the previous demonstration (Rodriquez-Aparicio, L. B., Guadalajara, A. M., and Rubio, V.(1989) Biochemistry 28, 3070-3074) that the C-terminal region is involved in binding AGA. Identification of peptides 120-127 and 234-237 constitutes the first evidence that the N-terminal region of the synthetase is involved in ligand binding. Since peptides 631-638 and 1327-1348 have been identified near the ATP site of CPSase I (Potter, M. D., and Powers-Lee, S. G.(1992) J. Biol. Chem. 267, 2023-2031), the present finding of involvement of peptides 625-630 and 1351-1356 at an "allosteric" activator site was unexpected. The idea that portions of the AGA effector site might be derived from an ancestral glutamine substrate site via a gene duplication and diversification event was considered.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cps1Ratglutamate binding  IPIPubChem_Compound:185 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cps1  (carbamoyl-phosphate synthase 1)


Additional Information