Abstract
Gamma-Glutamyl transpeptidase, which consists of two nonidentical subunits, is rapidly inactivated with respect to its transpeptidase and hydrolase activities by the gamma-glutamyl analogs 6-diazo-5-oxo-L-norleucine and L-azaserine. Inactivation, which is prevented by gamma-glutamyl substrates (but not by acceptor substrates), is accelerated by maleate, which was previously shown to enhance utilization of glutamine by transpeptidase. 6-Diazo-5-oxo--norleucine reacts specifically, covalently, and stoichiometrically at the gamma-glutamyl site of the enzyme, which was localized through studies with 6-diazo-5-OXO-[14C]norleucine to the light subunits of both the transpeptidase of rat kidney (which has subunits of molecular weights 22,000 and 46,000) and the transpeptidase of human kidney (which has subunits of molecular weights 22,000 and 62,000). The findings, which indicate that these enzymes have similar gamma-glutamyl binding subunits, are relevant to the structure-function relationships of this membrane-bound enzyme and its physiological role.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Buchanan J. M. The amidotransferases. Adv Enzymol Relat Areas Mol Biol. 1973;39:91–183. doi: 10.1002/9780470122846.ch2. [DOI] [PubMed] [Google Scholar]
- Gass J. D., Meister A. Computer analysis of the active site of glutamine synthetase. Biochemistry. 1970 Mar 17;9(6):1380–1390. doi: 10.1021/bi00808a012. [DOI] [PubMed] [Google Scholar]
- HARTMAN S. C. THE INTERACTION OF 6-DIAZO-5-OXO-L-NORLEUCINE WITH PHOSPHORIBOSYL PYROPHOSPHATE AMIDOTRANSFERASE. J Biol Chem. 1963 Sep;238:3036–3047. [PubMed] [Google Scholar]
- Horowitz B., Meister A. Glutamine-dependent asparagine synthetase from leukemia cells. Chloride dependence, mechanism of action, and inhibition. J Biol Chem. 1972 Oct 25;247(20):6708–6719. [PubMed] [Google Scholar]
- Jayaram H. N., Cooney D. A., Milman H. A., Homan E. R., Rosenbluth R. J. Don, conv and donv--I. Inhibition of L-asparagine synthetase in vitro. Biochem Pharmacol. 1976 Jul 15;25(14):1571–1582. doi: 10.1016/0006-2952(76)90466-4. [DOI] [PubMed] [Google Scholar]
- KITZ R., WILSON I. B. Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem. 1962 Oct;237:3245–3249. [PubMed] [Google Scholar]
- Khedouri E., Anderson P. M., Meister A. Selective inactivation of the glutamine binding site of Escherichia coli carbamyl phosphate synthetase by 2-amino-4-oxo-5-chloropentanoic acid. Biochemistry. 1966 Nov;5(11):3552–3557. doi: 10.1021/bi00875a024. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Levitzki A., Stallcup W. B., Koshland D. E., Jr Half-of-the-sites reactivity and the conformational states of cytidine triphosphate synthetase. Biochemistry. 1971 Aug 31;10(18):3371–3378. doi: 10.1021/bi00794a009. [DOI] [PubMed] [Google Scholar]
- Long C. W., Levitzki A., Koshland D. E., Jr The subunit structure and subunit interactions of cytidine triphosphate synthetase. J Biol Chem. 1970 Jan 10;245(1):80–87. [PubMed] [Google Scholar]
- Meister A. On the enzymology of amino acid transport. Science. 1973 Apr 6;180(4081):33–39. doi: 10.1126/science.180.4081.33. [DOI] [PubMed] [Google Scholar]
- Meister A., Tate S. S. Glutathione and related gamma-glutamyl compounds: biosynthesis and utilization. Annu Rev Biochem. 1976;45:559–604. doi: 10.1146/annurev.bi.45.070176.003015. [DOI] [PubMed] [Google Scholar]
- Meister A. The specificity of glutamine synthetase and its relationship to substrate conformation at the active site. Adv Enzymol Relat Areas Mol Biol. 1968;31:183–218. doi: 10.1002/9780470122761.ch5. [DOI] [PubMed] [Google Scholar]
- Novogrodsky A., Tate S. S., Meister A. gamma-Glutamyl transpeptidase, a lymphoid cell-surface marker: relationship to blastogenesis, differentiation, and neoplasia. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2414–2418. doi: 10.1073/pnas.73.7.2414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orlowski M., Meister A. The gamma-glutamyl cycle: a possible transport system for amino acids. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1248–1255. doi: 10.1073/pnas.67.3.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palekar A. G., Tate S. S., Meister A. Decrease in glutathione levels of kidney and liver after injection of methionine sulfoximine into rats. Biochem Biophys Res Commun. 1975 Feb 3;62(3):651–657. doi: 10.1016/0006-291x(75)90448-9. [DOI] [PubMed] [Google Scholar]
- Pinkus L. M., Meister A. Identification of a reactive cysteine residue at the glutamine binding site of carbamyl phosphate synthetase. J Biol Chem. 1972 Oct 10;247(19):6119–6127. [PubMed] [Google Scholar]
- Tate S. S., Meister A. Identity of maleate-stimulated glutaminase with gamma-glutamyl transpeptidase in rat kidney. J Biol Chem. 1975 Jun 25;250(12):4619–4627. [PubMed] [Google Scholar]
- Tate S. S., Meister A. Interaction of gamma-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione. J Biol Chem. 1974 Dec 10;249(23):7593–7602. [PubMed] [Google Scholar]
- Tate S. S., Meister A. Stimulation of the hydrolytic activity and decrease of the transpeptidase activity of gamma-glutamyl transpeptidase by maleate; identity of a rat kidney maleate-stimulated glutaminase and gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3329–3333. doi: 10.1073/pnas.71.9.3329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tate S. S., Meister A. Subunit structure and isozymic forms of gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2599–2603. doi: 10.1073/pnas.73.8.2599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thompson G. A., Meister A. Hydrolysis and transfer reactions catalyzed by gamma-glutamyl transpeptidase; evidence for separate substrate sites and for high affinity of L-cystine. Biochem Biophys Res Commun. 1976 Jul 12;71(1):32–36. doi: 10.1016/0006-291x(76)90245-x. [DOI] [PubMed] [Google Scholar]
- Zalkin H. Anthranilate synthetase. Adv Enzymol Relat Areas Mol Biol. 1973;38:1–39. doi: 10.1002/9780470122839.ch1. [DOI] [PubMed] [Google Scholar]