Back to Search
Start Over
Regulation of skeletal-muscle AMP deaminase: involvement of histidine residues in the pH-dependent inhibition of the rabbit enzyme by ATP.
- Source :
-
The Biochemical journal [Biochem J] 1995 Aug 01; Vol. 309 ( Pt 3), pp. 845-52. - Publication Year :
- 1995
-
Abstract
- Reaction of rabbit skeletal-muscle AMP deaminase with a low molar excess of diethyl pyrocarbonate results in conversion of the enzyme into a species with one or two carbethoxylated histidine residues per subunit that retains sensitivity to ATP at pH 7.1 but, unlike the native enzyme, it is not sensitive to regulation by ATP at pH 6.5. This effect mimics that exerted on the enzyme by limited proteolysis with trypsin, which removes the 95-residue N-terminal region from the 80 kDa enzyme subunit. These observations suggest involvement of some histidine residues localized in the region HHEMQAHILH (residues 51-60) in the regulatory mechanism which stabilizes the binding of ATP to its inhibitory site at acidic pH. Carbethoxylation of two histidine residues per subunit abolishes the inhibition by ATP of the proteolysed enzyme at pH 7.1, suggesting the obligatory participation of a second class of histidine residues, localized in the 70 kDa subunit core, in the mechanism of the pH-dependent inhibition of the enzyme by ATP. At a slightly acidic pH, these histidine residues would be positively charged, resulting in a desensitized form of the enzyme similar to that obtained with the carbethoxylation reaction.
- Subjects :
- AMP Deaminase antagonists & inhibitors
AMP Deaminase chemistry
Allosteric Regulation
Amino Acid Sequence
Animals
Diethyl Pyrocarbonate metabolism
Guanosine Triphosphate pharmacology
Hydrogen-Ion Concentration
Molecular Sequence Data
Rabbits
Trypsin pharmacology
AMP Deaminase metabolism
Adenosine Triphosphate pharmacology
Histidine metabolism
Muscle, Skeletal enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 309 ( Pt 3)
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 7639701
- Full Text :
- https://doi.org/10.1042/bj3090845