1r18
From Proteopedia
(New page: 200px<br /><applet load="1r18" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r18, resolution 2.20Å" /> '''Drosophila protein i...) |
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| - | [[Image:1r18.jpg|left|200px]]<br /><applet load="1r18" size=" | + | [[Image:1r18.jpg|left|200px]]<br /><applet load="1r18" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1r18, resolution 2.20Å" /> | caption="1r18, resolution 2.20Å" /> | ||
'''Drosophila protein isoaspartyl methyltransferase with S-adenosyl-L-homocysteine'''<br /> | '''Drosophila protein isoaspartyl methyltransferase with S-adenosyl-L-homocysteine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein L-isoaspartyl methyltransferases (PIMT; EC 2.1.1.77) catalyze the | + | Protein L-isoaspartyl methyltransferases (PIMT; EC 2.1.1.77) catalyze the S-adenosylmethionine-dependent methylation of L-isoaspartyl residues that arise spontaneously in proteins with age, thereby initiating a repair process that restores the normal backbone configuration to the damaged polypeptide. In Drosophila melanogaster, overexpression of PIMT in transgenic flies extends the normal life span, suggesting that protein damage can be a limiting factor in longevity. To understand structural features of the Drosophila PIMT (dPIMT) important for catalysis, the crystal structure of dPIMT was determined at a resolution of 2.2 A, and site-directed mutagenesis was used to identify the role of Ser-60 in catalysis. The core structure of dPIMT is similar to the modified nucleotide-binding fold observed in PIMTs from extreme thermophiles and humans. A striking difference of the dPIMT structure is the rotation of the C-terminal residues by 90 degrees relative to the homologous structures. Effectively, this displacement generates a more open conformation that allows greater solvent access to S-adenosylhomocysteine, which is almost completely buried in other PIMT structures. The enzyme may alternate between the open conformation found for dPIMT and the more closed conformations described for other PIMTs during its catalytic cycle, thereby allowing the exchange of substrates and products. Catalysis by dPIMT requires the side chain of the conserved, active site residue Ser-60, since substitution of this residue with Thr, Gln, or Ala reduces or abolishes the methylation of both protein and isoaspartyl peptide substrates. |
==About this Structure== | ==About this Structure== | ||
| - | 1R18 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with SAH as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-L-isoaspartate(D-aspartate)_O-methyltransferase Protein-L-isoaspartate(D-aspartate) O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.77 2.1.1.77] Full crystallographic information is available from [http:// | + | 1R18 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-L-isoaspartate(D-aspartate)_O-methyltransferase Protein-L-isoaspartate(D-aspartate) O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.77 2.1.1.77] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R18 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein-L-isoaspartate(D-aspartate) O-methyltransferase]] | [[Category: Protein-L-isoaspartate(D-aspartate) O-methyltransferase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bennett, E | + | [[Category: Bennett, E J.]] |
[[Category: Bjerregaard, J.]] | [[Category: Bjerregaard, J.]] | ||
| - | [[Category: Chavous, D | + | [[Category: Chavous, D A.]] |
| - | [[Category: Connor, C | + | [[Category: Connor, C M.O.]] |
| - | [[Category: Friedman, A | + | [[Category: Friedman, A M.]] |
| - | [[Category: Jr., W | + | [[Category: Jr., W E.Royer.]] |
| - | [[Category: Knapp, J | + | [[Category: Knapp, J E.]] |
[[Category: SAH]] | [[Category: SAH]] | ||
[[Category: isomerization]] | [[Category: isomerization]] | ||
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[[Category: s-adenosyl homocysteine]] | [[Category: s-adenosyl homocysteine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:45:55 2008'' |
Revision as of 12:45, 21 February 2008
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Drosophila protein isoaspartyl methyltransferase with S-adenosyl-L-homocysteine
Overview
Protein L-isoaspartyl methyltransferases (PIMT; EC 2.1.1.77) catalyze the S-adenosylmethionine-dependent methylation of L-isoaspartyl residues that arise spontaneously in proteins with age, thereby initiating a repair process that restores the normal backbone configuration to the damaged polypeptide. In Drosophila melanogaster, overexpression of PIMT in transgenic flies extends the normal life span, suggesting that protein damage can be a limiting factor in longevity. To understand structural features of the Drosophila PIMT (dPIMT) important for catalysis, the crystal structure of dPIMT was determined at a resolution of 2.2 A, and site-directed mutagenesis was used to identify the role of Ser-60 in catalysis. The core structure of dPIMT is similar to the modified nucleotide-binding fold observed in PIMTs from extreme thermophiles and humans. A striking difference of the dPIMT structure is the rotation of the C-terminal residues by 90 degrees relative to the homologous structures. Effectively, this displacement generates a more open conformation that allows greater solvent access to S-adenosylhomocysteine, which is almost completely buried in other PIMT structures. The enzyme may alternate between the open conformation found for dPIMT and the more closed conformations described for other PIMTs during its catalytic cycle, thereby allowing the exchange of substrates and products. Catalysis by dPIMT requires the side chain of the conserved, active site residue Ser-60, since substitution of this residue with Thr, Gln, or Ala reduces or abolishes the methylation of both protein and isoaspartyl peptide substrates.
About this Structure
1R18 is a Single protein structure of sequence from Drosophila melanogaster with as ligand. Active as Protein-L-isoaspartate(D-aspartate) O-methyltransferase, with EC number 2.1.1.77 Full crystallographic information is available from OCA.
Reference
Catalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis., Bennett EJ, Bjerregaard J, Knapp JE, Chavous DA, Friedman AM, Royer WE Jr, O'Connor CM, Biochemistry. 2003 Nov 11;42(44):12844-53. PMID:14596598
Page seeded by OCA on Thu Feb 21 14:45:55 2008
Categories: Drosophila melanogaster | Protein-L-isoaspartate(D-aspartate) O-methyltransferase | Single protein | Bennett, E J. | Bjerregaard, J. | Chavous, D A. | Connor, C M.O. | Friedman, A M. | Jr., W E.Royer. | Knapp, J E. | SAH | Isomerization | Methyltransferase | Protein repair | S-adenosyl homocysteine
