EzCatDB: D00823
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DB codeD00823
RLCP classification3.717.19970.25 : Transfer
CATH domainDomain 13.40.50.150 : Rossmann foldCatalytic domain
Domain 23.55.20.10 : Protein-l-isoaspartate O-methyltransferase; Chain
E.C.2.1.1.77

CATH domainRelated DB codes (homologues)
3.40.50.150 : Rossmann foldS00637,S00639,S00262,S00261,S00291,S00412,D00075,D00076,D00079,D00080,D00082,D00083

Enzyme Name
UniProtKBKEGG

Q56308
Protein nameProtein-L-isoaspartate O-methyltransferaseProtein-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
SynonymsEC 2.1.1.77
L-isoaspartyl protein carboxyl methyltransferase
Protein L-isoaspartyl methyltransferase
Protein-beta-aspartate methyltransferase
PIMT
RefSeqNP_228513.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PfamPF01135 (PCMT)
[Graphical view]


UniProtKB:Accession NumberQ56308
Entry namePIMT_THEMA
ActivityS-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester.
SubunitMonomer.
Subcellular locationCytoplasm (By similarity).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00019C03306C00021C04311
CompoundS-adenosyl-L-methionineprotein L-isoaspartateS-adenosyl-L-homocysteineprotein L-isoaspartate alpha-methyl ester
Typeamino acids,amine group,nucleoside,sulfonium ioncarboxyl group,peptide/proteinamino acids,amine group,nucleoside,sulfide groupcarbohydrate,peptide/protein
ChEBI67040

16680
57856

PubChem34755

439155
25246222

            
1dl5A01UnboundUnboundBound:SAHUnbound
1dl5B01UnboundUnboundBound:SAHUnbound
1dl5A02UnboundUnboundUnboundUnbound
1dl5B02UnboundUnboundUnboundUnbound

Active-site residues
resource
literature [2], [7] & Swiss;Q56308
pdbCatalytic residues
         
1dl5A01SER 59
1dl5B01SER 59
1dl5A02      
1dl5B02      

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.5c, p.1196-1198
[7]p.12850-12852

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 11-284
PubMed ID9115443
JournalStructure
Year1997
Volume5
Pages545-58
AuthorsDjordjevic S, Stock AM
TitleCrystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine.
Related PDB1af7
Related UniProtKBP07801
[2]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
PubMed ID11080641
JournalStructure
Year2000
Volume8
Pages1189-201
AuthorsSkinner MM, Puvathingal JM, Walter RL, Friedman AM
TitleCrystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.
Related PDB1dl5
Related UniProtKBQ56308
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS).
PubMed ID11700066
JournalJ Mol Biol
Year2001
Volume313
Pages1103-16
AuthorsGriffith SC, Sawaya MR, Boutz DR, Thapar N, Katz JE, Clarke S, Yeates TO
TitleCrystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate.
Related PDB1jg1,1jg2,1jg3,1jg4
Related UniProtKBQ8TZR3
[4]
PubMed ID12504684
JournalCurr Opin Struct Biol
Year2002
Volume12
Pages783-93
AuthorsMartin JL, McMillan FM
TitleSAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol. 2002 Dec;12(6):783-93. Review.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
PubMed ID11792715
JournalJ Biol Chem
Year2002
Volume277
Pages10642-6
AuthorsRyttersgaard C, Griffith SC, Sawaya MR, MacLaren DC, Clarke S, Yeates TO
TitleCrystal structure of human L-isoaspartyl methyltransferase.
Related PDB1kr5
Related UniProtKBP22061
[6]
CommentsX-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
PubMed ID11847284
JournalProtein Sci
Year2002
Volume11
Pages625-35
AuthorsSmith CD, Carson M, Friedman AM, Skinner MM, Delucas L, Chantalat L, Weise L, Shirasawa T, Chattopadhyay D
TitleCrystal 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 PDB1i1n
Related UniProtKBP22061
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-221, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF SER-60.
PubMed ID14596598
JournalBiochemistry
Year2003
Volume42
Pages12844-53
AuthorsBennett EJ, Bjerregaard J, Knapp JE, Chavous DA, Friedman AM, Royer WE Jr, O'Connor CM
TitleCatalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis.
Related PDB1r18
Related UniProtKBQ27869

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.

createdupdated
2009-10-282010-08-19


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