Journal:Acta Cryst D:S2059798319000676
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L-pyroglutamate (pG) is formed by the cyclization of the side chain of glutamate or glutamine amino acid with alpha-amino group at the N-terminus of a polypeptide. This modified residue (pG) cannot be removed by any of the conventional peptidases. Special type of aminopeptidases called pyrrolidone-carboxylate peptidases (PCPs) (EC 3.4.19.-) can remove this unusual amino acid from the peptides or proteins. PCPs are of two types, a) PCPs I, which are cysteine peptidases of C15 family, b) PCPs II are metallopeptidases of M1 family. PCP I is highly conserved enzyme and its homologs have been found from bacteria to human. Many of the physiologically important peptide hormones (TRH, LHRH, GnRH) and antibodies have been shown to possess the pG residue at their N-termini. It seems to have implications in functional regulation of different peptides in both prokaryotes and eukaryotes. However, how these class of enzymes specifically catalyse the removal of pG residue remains mostly unknown. The crystal structures of PCP I from ''Deinococcus radiodurans'' (PCPdr) in its pG-free and pG-bound forms at high resolutions has helped to solve this puzzle. | L-pyroglutamate (pG) is formed by the cyclization of the side chain of glutamate or glutamine amino acid with alpha-amino group at the N-terminus of a polypeptide. This modified residue (pG) cannot be removed by any of the conventional peptidases. Special type of aminopeptidases called pyrrolidone-carboxylate peptidases (PCPs) (EC 3.4.19.-) can remove this unusual amino acid from the peptides or proteins. PCPs are of two types, a) PCPs I, which are cysteine peptidases of C15 family, b) PCPs II are metallopeptidases of M1 family. PCP I is highly conserved enzyme and its homologs have been found from bacteria to human. Many of the physiologically important peptide hormones (TRH, LHRH, GnRH) and antibodies have been shown to possess the pG residue at their N-termini. It seems to have implications in functional regulation of different peptides in both prokaryotes and eukaryotes. However, how these class of enzymes specifically catalyse the removal of pG residue remains mostly unknown. The crystal structures of PCP I from ''Deinococcus radiodurans'' (PCPdr) in its pG-free and pG-bound forms at high resolutions has helped to solve this puzzle. | ||
| - | <scene name='80/806393/Cv/5'>A Ribbon diagram of PCPdr monomer</scene> (spectrum color) is shown in cartoon with pG bound to the active site shown in magenta ball-and-sticks. | + | <scene name='80/806393/Cv/5'>A Ribbon diagram of PCPdr monomer</scene> (spectrum color) is shown in cartoon with pG bound to the active site shown in magenta ball-and-sticks. Briefly, the monomeric structure of PCPdr consists of a single α/β fold in which a twisted seven-stranded mixed β-sheet (β1-β5, β8, and β9) is flanked by two α helices on one side (α2, and α4) and three α helices (α1, α3, and α6) on other side. |
Residues responsible for recognizing pG residue are mostly contributed by a flexible loop (loop-A), present near the active site. Phenylalanine residues of loop-A form stacking interactions with the pyrrolidone ring of pG, while Asn18 forms a hydrogen bond with OE of pG. These residues are conserved in all the known PCPs I, including those from mammals. The pG residue of peptides is recognized in the S1 substrate subsite of the enzyme by both van der Waals, and polar interactions, which provide specificity for the pG residue of the peptide. | Residues responsible for recognizing pG residue are mostly contributed by a flexible loop (loop-A), present near the active site. Phenylalanine residues of loop-A form stacking interactions with the pyrrolidone ring of pG, while Asn18 forms a hydrogen bond with OE of pG. These residues are conserved in all the known PCPs I, including those from mammals. The pG residue of peptides is recognized in the S1 substrate subsite of the enzyme by both van der Waals, and polar interactions, which provide specificity for the pG residue of the peptide. | ||
Revision as of 12:41, 23 January 2019
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
