{PDOC00329} {PS00392; DDC_GAD_HDC_YDC} {BEGIN} *************************************************************** * DDC / GAD / HDC / TyrDC pyridoxal-phosphate attachment site * *************************************************************** Three different enzymes - all pyridoxal-dependent decarboxylases - seem to share regions of sequence similarity [1,2,3,4], especially in the vicinity of the lysine residue which serves as the attachment site for the pyridoxal- phosphate (PLP) group. These enzymes are: - Glutamate decarboxylase (EC 4.1.1.15) (GAD). Catalyzes the decarboxylation of glutamate into the neurotransmitter GABA (4-aminobutanoate). - Histidine decarboxylase (EC 4.1.1.22) (HDC). Catalyzes the decarboxylation of histidine to histamine. There are two completely unrelated types of HDC: those that use PLP as a cofactor (found in Gram-negative bacteria and mammals), and those that contain a covalently bound pyruvoyl residue (found in Gram-positive bacteria). - Aromatic-L-amino-acid decarboxylase (EC 4.1.1.28) (DDC), also known as L-dopa decarboxylase or tryptophan decarboxylase. DDC catalyzes the decarboxylation of tryptophan to tryptamine. It also acts on 5-hydroxy- tryptophan and dihydroxyphenylalanine (L-dopa). - Tyrosine decarboxylase (EC 4.1.1.25) (TyrDC) which converts tyrosine into tyramine, a precursor of isoquinoline alkaloids and various amides. - Cysteine sulfinic acid decarboxylase (EC 4.1.1.29). - L-2,4-diaminobutyrate decarboxylase (EC 4.1.1.-) (DABA decarboxylase). These enzymes are collectively known as group II decarboxylases [3,4]. -Consensus pattern: S-[LIVMFYW]-x-{KG}-x(3)-K-[LIVMFYWGH]-[LIVMFYWG]-x-{R}-x- [LIVMFYW]-{V}-[CA]-x(2)-[LIVMFYWQ]-{K}-x-[RK] [K is the pyridoxal-P attachment site] -Sequences known to belong to this class detected by the pattern: ALL, except for a probable Caenorhabditis elegans DDC and for Petunia GAD. -Other sequence(s) detected in Swiss-Prot: 5. -Last update: April 2006 / Pattern revised. [ 1] Jackson F.R. "Prokaryotic and eukaryotic pyridoxal-dependent decarboxylases are homologous." J. Mol. Evol. 31:325-329(1990). PubMed=2124279 [ 2] Joseph D.R., Sullivan P.M., Wang Y.-M., Kozak C., Fenstermacher D.A., Behrendsen M.E., Zahnow C.A. "Characterization and expression of the complementary DNA encoding rat histidine decarboxylase." Proc. Natl. Acad. Sci. U.S.A. 87:733-737(1990). PubMed=2300558 [ 3] Sandmeier E., Hale T.I., Christen P. "Multiple evolutionary origin of pyridoxal-5'-phosphate-dependent amino acid decarboxylases." Eur. J. Biochem. 221:997-1002(1994). PubMed=8181483 [ 4] Ishii S., Mizuguchi H., Nishino J., Hayashi H., Kagamiyama H. "Functionally important residues of aromatic L-amino acid decarboxylase probed by sequence alignment and site-directed mutagenesis." J. Biochem. 120:369-376(1996). PubMed=8889823 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}