1JG3

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

Summary for 1JG3

• Entry DOI: 10.2210/pdb1jg3/pdb
• Descriptor: protein-L-isoaspartate O-methyltransferase, VYP(L-iso-ASP)HA, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: rossmann methyltransferase, protein repair isomerization, transferase
• Biological source: Pyrococcus furiosus
• Cellular location: Cytoplasm (By similarity): Q8TZR3
• Total number of polymer chains: 4
• Total formula weight: 55281.04

Authors

Griffith, S.C.,Sawaya, M.R.,Boutz, D.,Thapar, N.,Katz, J.,Clarke, S.,Yeates, T.O. (deposition date: 2001-06-22, release date: 2001-11-16, Last modification date: 2024-11-13)

Primary citation

Griffith, S.C.,Sawaya, M.R.,Boutz, D.R.,Thapar, N.,Katz, J.E.,Clarke, S.,Yeates, T.O.
Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate.
J.Mol.Biol., 313:1103-1116, 2001

PubMed Abstract: 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.

PubMed: 11700066
DOI: 10.1006/jmbi.2001.5095

Experimental method

X-RAY DIFFRACTION (2.1 Å)