1KR5

Crystal structure of human L-isoaspartyl methyltransferase

1KR5 の概要

• エントリーDOI: 10.2210/pdb1kr5/pdb
• 分子名称: Protein-L-isoaspartate O-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: rossmann-fold doubly-wound-alpha-beta-alpha-sandwich, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P22061
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24921.62

構造登録者

Ryttersgaard, C.,Griffith, S.C.,Sawaya, M.R.,MacLaren, D.C.,Clarke, S.,Yeates, T.O. (登録日: 2002-01-08, 公開日: 2002-02-08, 最終更新日: 2023-09-20)

主引用文献

Ryttersgaard, C.,Griffith, S.C.,Sawaya, M.R.,MacLaren, D.C.,Clarke, S.,Yeates, T.O.
Crystal structure of human L-isoaspartyl methyltransferase.
J.Biol.Chem., 277:10642-10646, 2002

PubMed Abstract: The enzyme l-isoaspartyl methyltransferase initiates the repair of damaged proteins by recognizing and methylating isomerized and racemized aspartyl residues in aging proteins. The crystal structure of the human enzyme containing a bound S-adenosyl-l-homocysteine cofactor is reported here at a resolution of 2.1 A. A comparison of the human enzyme to homologs from two other species reveals several significant differences among otherwise similar structures. In all three structures, we find that three conserved charged residues are buried in the protein interior near the active site. Electrostatics calculations suggest that these buried charges might make significant contributions to the energetics of binding the charged S-adenosyl-l-methionine cofactor and to catalysis. We suggest a possible structural explanation for the observed differences in reactivity toward the structurally similar l-isoaspartyl and d-aspartyl residues in the human, archael, and eubacterial enzymes. Finally, the human structure reveals that the known genetic polymorphism at residue 119 (Val/Ile) maps to an exposed region away from the active site.

PubMed: 11792715
DOI: 10.1074/jbc.M200229200

実験手法

X-RAY DIFFRACTION (2.1 Å)