1jg3: Difference between revisions

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Crystal Structure of L-isoaspartyl (D-aspartyl) O-methyltransferase with adenosine & VYP(ISP)HA substrate

OverviewOverview

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 StructureAbout this Structure

1JG3 is a Single protein structure of sequence from Pyrococcus furiosus with , and as ligands. Active as Protein-L-isoaspartate(D-aspartate) O-methyltransferase, with EC number 2.1.1.77 Full crystallographic information is available from OCA.

ReferenceReference

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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-[[Image:1jg3.jpg|left|200px]]<br /><applet load="1jg3" size="450" color="white" frame="true" align="right" spinBox="true"
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 '''Crystal Structure of L-isoaspartyl (D-aspartyl) O-methyltransferase with adenosine & VYP(ISP)HA substrate'''<br />
 ==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.
+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==
-JG3 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 CL, NA and ADN as [http://en.wikipedia.org/wiki/ligands ligands]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JG3 OCA].
+JG3 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=CL:'>CL</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=ADN:'>ADN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1JG3 OCA].
 ==Reference==
@@ Line 16: / Line 16: @@
 [[Category: Boutz, D.]]
 [[Category: Clarke, S.]]
-[[Category: Griffith, S.C.]]
+[[Category: Griffith, S C.]]
 [[Category: Katz, J.]]
-[[Category: Sawaya, M.R.]]
+[[Category: Sawaya, M R.]]
 [[Category: Thapar, N.]]
-[[Category: Yeates, T.O.]]
+[[Category: Yeates, T O.]]
 [[Category: ADN]]
 [[Category: CL]]
@@ Line 27: / Line 27: @@
 [[Category: rossmann methyltransferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:12:56 2007''
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