Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.4.1.1 (
pyruvate carboxylase
)
1,516
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pyruvate carboxylase
is a highly conserved enzyme that functions in replenishing the tricarboxylic acid cycle with oxaloacetate. In the yeast Hansenulapolymorpha, the
pyruvate carboxylase
protein is also required for import and assembly of the peroxisomal enzyme alcohol oxidase. This additional role, which is unrelated to the enzyme activity, represents an example of a special form of multifunctionality called moonlighting. We have performed a detailed site-directed mutagenesis approach to elucidate which region(s) of H. polymorpha
pyruvate carboxylase
are involved in its second function. This resulted in the identification of three amino acids that are essential for the moonlighting function. Mutating these residues in a single mutant protein fully inactivated the moonlighting function, but not the enzyme activity of
pyruvate carboxylase
because the strain was prototrophic. A 3D homology model revealed that all three residues are positioned at the side of a
TIM
barrel where the N-terminal ends of the beta-strands are located. This is a novel observation as the
TIM
barrel proteins invariably are enzymes and have their catalytic side at the C-terminal end of the beta-sheets. Our finding implies that a
TIM
barrel fold can also fulfill a non-enzymatic function and that this function can reside at the N-terminal end of the barrel.
...
PMID:The moonlighting function of pyruvate carboxylase resides in the non-catalytic end of the TIM barrel. 2035 4
