Journal:Acta Cryst D:S2059798319000676
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
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. | ||
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| + | <scene name='80/806393/Cv/23'>Tetrameric structure of PCPdr is shown in cartoon representation</scene>. Each monomer is shown in different color. Bound substrate is shown in magenta spacefill representation. This tetrameric structure is similar to those observed in other PCP I proteins and buries equivalent surfaces of monomers for the formations of the tetramers. | ||
<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. The active site is entirely formed by residues from only one monomeric subunit. It is located at the depression which is formed by the protruding loops of the α/β core of the protein. These loops are <scene name='80/806393/Cv/6'>loop-A (residues 9-19), loop-B (residues 85-112) and loop-C (residues 178-192)</scene> which could play an important role in substrate entry. The residues of <scene name='80/806393/Cv/7'>the catalytic triad, Cys144, Glu81 and His169</scene>, are located at the N-terminus of helix α4, C-terminus of strand β5 and C-terminus of strand β11, respectively. | <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. The active site is entirely formed by residues from only one monomeric subunit. It is located at the depression which is formed by the protruding loops of the α/β core of the protein. These loops are <scene name='80/806393/Cv/6'>loop-A (residues 9-19), loop-B (residues 85-112) and loop-C (residues 178-192)</scene> which could play an important role in substrate entry. The residues of <scene name='80/806393/Cv/7'>the catalytic triad, Cys144, Glu81 and His169</scene>, are located at the N-terminus of helix α4, C-terminus of strand β5 and C-terminus of strand β11, respectively. | ||
Revision as of 11:17, 24 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.
