1jg3
From Proteopedia
|
Crystal Structure of L-isoaspartyl (D-aspartyl) O-methyltransferase with adenosine & VYP(ISP)HA substrate
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
1JG3 is a Single protein structure of sequence from Pyrococcus furiosus with CL, NA and ADN 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.
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
Page seeded by OCA on Tue Nov 20 18:12:56 2007
