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Crystal structure of human L-isoaspartyl methyltransferase.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Mar 22; Vol. 277 (12), pp. 10642-6. Date of Electronic Publication: 2002 Jan 15. - Publication Year :
- 2002
-
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.
- Subjects :
- Binding Sites
Catalysis
Conserved Sequence
Crystallography, X-Ray
Humans
Leucine chemistry
Models, Molecular
Polymorphism, Genetic
Protein Binding
Protein Conformation
Protein D-Aspartate-L-Isoaspartate Methyltransferase metabolism
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
RNA, Messenger metabolism
Protein D-Aspartate-L-Isoaspartate Methyltransferase chemistry
Protein D-Aspartate-L-Isoaspartate Methyltransferase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11792715
- Full Text :
- https://doi.org/10.1074/jbc.M200229200