DB code: D00823

RLCP classification 3.717.19970.25 : Transfer
CATH domain 3.40.50.150 : Rossmann fold Catalytic domain
3.55.20.10 : Protein-l-isoaspartate O-methyltransferase; Chain
E.C. 2.1.1.77
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.150 : Rossmann fold S00637 S00639 S00262 S00261 S00291 S00412 D00075 D00076 D00079 D00080 D00082 D00083

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q56308 Protein-L-isoaspartate O-methyltransferase
EC 2.1.1.77
L-isoaspartyl protein carboxyl methyltransferase
Protein L-isoaspartyl methyltransferase
Protein-beta-aspartate methyltransferase
PIMT
NP_228513.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PF01135 (PCMT)
[Graphical View]

KEGG enzyme name
Protein-L-isoaspartate(D-aspartate) O-methyltransferase
Protein-L-isoaspartate O-methyltransferase
Protein-beta-aspartate O-methyltransferase
D-Aspartyl/L-isoaspartyl methyltransferase
L-Isoaspartyl/D-aspartyl protein carboxyl methyltransferase
Protein (D-aspartate) methyltransferase
Protein D-aspartate methyltransferase
Protein L-isoaspartate methyltransferase
Protein L-isoaspartyl methyltransferase
Protein O-methyltransferase (L-isoaspartate)
L-Aspartyl/L-isoaspartyl protein methyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q56308 PIMT_THEMA S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester. Monomer. Cytoplasm (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00019 C03306 C00021 C04311
E.C.
Compound S-adenosyl-L-methionine protein L-isoaspartate S-adenosyl-L-homocysteine protein L-isoaspartate alpha-methyl ester
Type amino acids,amine group,nucleoside,sulfonium ion carboxyl group,peptide/protein amino acids,amine group,nucleoside,sulfide group carbohydrate,peptide/protein
ChEBI 67040
16680
57856
PubChem 34755
25246222
439155
1dl5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1dl5B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1dl5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1dl5B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [7] & Swiss;Q56308

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dl5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 59
1dl5B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 59
1dl5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1dl5B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.5c, p.1196-1198
[7]
p.12850-12852

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 11-284
Medline ID
PubMed ID 9115443
Journal Structure
Year 1997
Volume 5
Pages 545-58
Authors Djordjevic S, Stock AM
Title Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine.
Related PDB 1af7
Related UniProtKB P07801
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID
PubMed ID 11080641
Journal Structure
Year 2000
Volume 8
Pages 1189-201
Authors Skinner MM, Puvathingal JM, Walter RL, Friedman AM
Title Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.
Related PDB 1dl5
Related UniProtKB Q56308
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS).
Medline ID
PubMed ID 11700066
Journal J Mol Biol
Year 2001
Volume 313
Pages 1103-16
Authors Griffith SC, Sawaya MR, Boutz DR, Thapar N, Katz JE, Clarke S, Yeates TO
Title Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate.
Related PDB 1jg1 1jg2 1jg3 1jg4
Related UniProtKB Q8TZR3
[4]
Resource
Comments
Medline ID
PubMed ID 12504684
Journal Curr Opin Struct Biol
Year 2002
Volume 12
Pages 783-93
Authors Martin JL, McMillan FM
Title SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol. 2002 Dec;12(6):783-93. Review.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID
PubMed ID 11792715
Journal J Biol Chem
Year 2002
Volume 277
Pages 10642-6
Authors Ryttersgaard C, Griffith SC, Sawaya MR, MacLaren DC, Clarke S, Yeates TO
Title Crystal structure of human L-isoaspartyl methyltransferase.
Related PDB 1kr5
Related UniProtKB P22061
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
Medline ID
PubMed ID 11847284
Journal Protein Sci
Year 2002
Volume 11
Pages 625-35
Authors Smith CD, Carson M, Friedman AM, Skinner MM, Delucas L, Chantalat L, Weise L, Shirasawa T, Chattopadhyay D
Title Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl homocysteine at 1.6-A resolution and modeling of an isoaspartyl-containing peptide at the active site.
Related PDB 1i1n
Related UniProtKB P22061
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-221, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF SER-60.
Medline ID
PubMed ID 14596598
Journal Biochemistry
Year 2003
Volume 42
Pages 12844-53
Authors Bennett EJ, Bjerregaard J, Knapp JE, Chavous DA, Friedman AM, Royer WE Jr, O'Connor CM
Title Catalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis.
Related PDB 1r18
Related UniProtKB Q27869

Comments
This enzyme catalyzes the repair of proteins, which are age-damaged by isomerized and racemized aspartyl residue leading to the isoaspartyl formation (L-isoAsp), by methylation of the alpha-carboxylate of isoAsp in the damaged peptide. The methyl ester product is unstable and rapidly converted to succinimide, which can form either the normal L-Asp residue or the L-isoAsp residue spontaneously.
This enzyme has homologous enzymes with a single domain (see S00639 in EzCatDB).
According to the literature [2] and [7], the reaction of this enzyme occurs as follows:
(1) Ser59 modulates the nucleophilicity of the alpha-carboxylate of the substrate, by orienting the oxygen atom of the acceptor carboxylate group, and by creating aprotic environment that is favorable for an SN2 reaction.
(2) The acceptor carboxylate group makes a nucleophilic attack on the methyl group on AdoMet. This is an SN2 reaction.

Created Updated
2009-10-28 2010-08-19