F
IPR017153

Cytosolic nonspecific dipeptidase/DUG1

InterPro entry
Short nameCNDP/DUG1
family relationships

Description

This peptidase M20 subfamily includes CNDP1 (beta-Ala-His dipeptidase), CNDP2 (cytosolic nonspecific dipeptidase) and DUG1 from yeast, which are metallopeptidases
[9, 1]
.

Two genes, CN1 and CN2, that degrade carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyric acid-L-histidine), two naturally occurring dipeptides with potential neuroprotective and neurotransmitter functions, have been identified. CN1 encodes for serum carnosinase and has narrow substrate specificity for Xaa-His dipeptides, where Xaa can be beta-alanine (carnosine), N-methyl beta-alanine, alanine, glycine and gamma-aminobutyric acid (homocarnosine). CN2 corresponds to the cytosolic nonspecific dipeptidase (CNDP2) and is not limited to Xaa-His dipeptides. CNDP2 requires Mn(2+) for full activity and does not hydrolyze homocarnosine
[4, 8, 7, 6, 3, 2]
.

Metallodipeptidase DUG1 is a subunit of the GSH degradosomal complex, involved in the degradation of glutathione (GSH) and other peptides containing a gamma-glu-X bond. Although dipeptides and tripeptides with a normal peptide bond, such as cys-gly or glu-cys-gly, can be hydrolysed by the DUG1 protein, the presence of an unusual peptide bond, such as in GSH, requires the participation of the DUG2 and DUG3 gene products as well. These three proteins form a GSH degradosomal complex
[5]
.

References

1.Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. Teufel M, Saudek V, Ledig JP, Bernhardt A, Boularand S, Carreau A, Cairns NJ, Carter C, Cowley DJ, Duverger D, Ganzhorn AJ, Guenet C, Heintzelmann B, Laucher V, Sauvage C, Smirnova T. J. Biol. Chem. 278, 6521-31, (2003). PMID: 12473676

2.The Zn-peptidase superfamily: functional convergence after evolutionary divergence. Makarova KS, Grishin NV. J. Mol. Biol. 292, 11-7, (1999). View articlePMID: 10493853

3.Homology modeling of human serum carnosinase, a potential medicinal target, and MD simulations of its allosteric activation by citrate. Vistoli G, Pedretti A, Cattaneo M, Aldini G, Testa B. J. Med. Chem. 49, 3269-77, (2006). View articlePMID: 16722645

4.Evolutionary families of metallopeptidases. Rawlings ND, Barrett AJ. Meth. Enzymol. 248, 183-228, (1995). View articlePMID: 7674922

5.The alternative pathway of glutathione degradation is mediated by a novel protein complex involving three new genes in Saccharomyces cerevisiae. Ganguli D, Kumar C, Bachhawat AK. Genetics 175, 1137-51, (2007). View articlePMID: 17179087

6.Purification and sequence identification of anserinase. Yamada S, Tanaka Y, Ando S. FEBS J. 272, 6001-13, (2005). View articlePMID: 16302965

7.Carnosine and carnosine-related antioxidants: a review. Guiotto A, Calderan A, Ruzza P, Borin G. Curr. Med. Chem. 12, 2293-315, (2005). View articlePMID: 16181134

8.Crystallization and preliminary crystallographic study of carnosinase CN2 from mice. Yamashita T, Unno H, Ujita S, Otani H, Okumura N, Hashida-Okumura A, Nagai K, Kusunoki M. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62, 996-8, (2006). View articlePMID: 17012794

9.Dug1p Is a Cys-Gly peptidase of the gamma-glutamyl cycle of Saccharomyces cerevisiae and represents a novel family of Cys-Gly peptidases. Kaur H, Kumar C, Junot C, Toledano MB, Bachhawat AK. J. Biol. Chem. 284, 14493-502, (2009). View articlePMID: 19346245

GO terms

biological process

  • None

cellular component

  • None

Cross References

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