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1jg4
From Proteopedia
(New page: 200px<br /><applet load="1jg4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jg4, resolution 1.5Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1jg4.jpg|left|200px]]<br /><applet load="1jg4" size=" | + | [[Image:1jg4.jpg|left|200px]]<br /><applet load="1jg4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jg4, resolution 1.5Å" /> | caption="1jg4, resolution 1.5Å" /> | ||
'''Crystal Structure of L-isoaspartyl (D-aspartyl) O-methyltransferase with S-adenosylmethionine'''<br /> | '''Crystal Structure of L-isoaspartyl (D-aspartyl) O-methyltransferase with S-adenosylmethionine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein L-isoaspartyl (D-aspartyl) methyltransferases (EC 2.1.1.77) are | + | Protein L-isoaspartyl (D-aspartyl) methyltransferases (EC 2.1.1.77) are found in almost all organisms. These enzymes catalyze the S-adenosylmethionine (AdoMet)-dependent methylation of isomerized and racemized aspartyl residues in age-damaged proteins as part of an essential protein repair process. Here, we report crystal structures of the repair methyltransferase at resolutions up to 1.2 A from the hyperthermophilic archaeon Pyrococcus furiosus. Refined structures include binary complexes with the active cofactor AdoMet, its reaction product S-adenosylhomocysteine (AdoHcy), and adenosine. The enzyme places the methyl-donating cofactor in a deep, electrostatically negative pocket that is shielded from solvent. Across the multiple crystal structures visualized, the presence or absence of the methyl group on the cofactor correlates with a significant conformational change in the enzyme in a loop bordering the active site, suggesting a role for motion in catalysis or cofactor exchange. We also report the structure of a ternary complex of the enzyme with adenosine and the methyl-accepting polypeptide substrate VYP(L-isoAsp)HA at 2.1 A. The substrate binds in a narrow active site cleft with three of its residues in an extended conformation, suggesting that damaged proteins may be locally denatured during the repair process in cells. Manual and computer-based docking studies on different isomers help explain how the enzyme uses steric effects to make the critical distinction between normal L-aspartyl and age-damaged L-isoaspartyl and D-aspartyl residues. |
==About this Structure== | ==About this Structure== | ||
| - | 1JG4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus] with SAM 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:// | + | 1JG4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus] with <scene name='pdbligand=SAM:'>SAM</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=1JG4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Boutz, D.]] | [[Category: Boutz, D.]] | ||
[[Category: Clarke, S.]] | [[Category: Clarke, S.]] | ||
| - | [[Category: Griffith, S | + | [[Category: Griffith, S C.]] |
[[Category: Katz, J.]] | [[Category: Katz, J.]] | ||
| - | [[Category: Sawaya, M | + | [[Category: Sawaya, M R.]] |
[[Category: Thapar, N.]] | [[Category: Thapar, N.]] | ||
| - | [[Category: Yeates, T | + | [[Category: Yeates, T O.]] |
[[Category: SAM]] | [[Category: SAM]] | ||
[[Category: protein repair isomerization]] | [[Category: protein repair isomerization]] | ||
[[Category: rossmann methyltransferase]] | [[Category: rossmann methyltransferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:22:17 2008'' |
Revision as of 11:22, 21 February 2008
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Crystal Structure of L-isoaspartyl (D-aspartyl) O-methyltransferase with S-adenosylmethionine
Overview
Protein L-isoaspartyl (D-aspartyl) methyltransferases (EC 2.1.1.77) are found in almost all organisms. These enzymes catalyze the S-adenosylmethionine (AdoMet)-dependent methylation of isomerized and racemized aspartyl residues in age-damaged proteins as part of an essential protein repair process. Here, we report crystal structures of the repair methyltransferase at resolutions up to 1.2 A from the hyperthermophilic archaeon Pyrococcus furiosus. Refined structures include binary complexes with the active cofactor AdoMet, its reaction product S-adenosylhomocysteine (AdoHcy), and adenosine. The enzyme places the methyl-donating cofactor in a deep, electrostatically negative pocket that is shielded from solvent. Across the multiple crystal structures visualized, the presence or absence of the methyl group on the cofactor correlates with a significant conformational change in the enzyme in a loop bordering the active site, suggesting a role for motion in catalysis or cofactor exchange. We also report the structure of a ternary complex of the enzyme with adenosine and the methyl-accepting polypeptide substrate VYP(L-isoAsp)HA at 2.1 A. The substrate binds in a narrow active site cleft with three of its residues in an extended conformation, suggesting that damaged proteins may be locally denatured during the repair process in cells. Manual and computer-based docking studies on different isomers help explain how the enzyme uses steric effects to make the critical distinction between normal L-aspartyl and age-damaged L-isoaspartyl and D-aspartyl residues.
About this Structure
1JG4 is a Single protein structure of sequence from Pyrococcus furiosus 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
Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate., Griffith SC, Sawaya MR, Boutz DR, Thapar N, Katz JE, Clarke S, Yeates TO, J Mol Biol. 2001 Nov 9;313(5):1103-16. PMID:11700066
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