|PROSITE documentation PDOC00678|
Renal dipeptidase (rDP) (EC 126.96.36.199), also known as microsomal dipeptidase or membrane dipeptidase, is a zinc-dependent metalloenzyme which hydrolyzes a wide range of dipeptides. It is involved in renal metabolism of glutathione and its conjugates. It is a homodimeric disulfide-linked glycoprotein attached to the renal brush border microvilli membrane by a GPI-anchor.
The active site of rDP is composed of binuclear zinc ions bridged by a glutamate residue [1,2]. The two zinc ions are coordinated by three different histidine residues, the glutamate and an aspartate (see <PDB:1ITU>). Four cysteine residues form two disulfide bonds and an additional cysteine residue in the C-terminal part links to the corresponding cysteine of the other subunit in the homodimeric enzyme.
RDP seems to be evolutionary related to hypothetical proteins in the PQQ biosynthesis operons of Acinetobacter calcoaceticus and Klebsiella pneumoniae. We selected for a signature pattern the region around the glutamate residue in the active site, which is highly conserved. We also developed a profile that covers the entire renal dipeptidase.Last update:
February 2008 / Text revised; profile added.Note:
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Adachi H., Katayama T., Nakazato H., Tsujimoto M.|
|Title||Importance of Glu-125 in the catalytic activity of human renal dipeptidase.|
|Source||Biochim. Biophys. Acta 1163:42-48(1993).|
|2||Authors||Nitanai Y., Satow Y., Adachi H., Tsujimoto M.|
|Title||Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.|
|Source||J. Mol. Biol. 321:177-184(2002).|
|3||Authors||Rawlings N.D., Barrett A.J.|
|Title||Evolutionary families of metallopeptidases.|
|Source||Methods Enzymol. 248:183-228(1995).|