EzCatDB: S00639
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00639
RLCP classification3.717.19970.25 : Transfer
CATH domainDomain 13.40.50.150 : Rossmann foldCatalytic domain
E.C.2.1.1.77

CATH domainRelated DB codes (homologues)
3.40.50.150 : Rossmann foldS00637,S00262,S00261,S00291,S00412,D00075,D00076,D00079,D00080,D00082,D00083,D00823

Enzyme Name
UniProtKBKEGG

Q57636Q8TZR3Q8ILD5Q27869P22061
Protein nameProtein-L-isoaspartate O-methyltransferaseProtein-L-isoaspartate O-methyltransferase
Protein-L-isoaspartate(D-aspartate) O-methyltransferaseProtein-L-isoaspartate(D-aspartate) 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
Protein-beta-aspartate methyltransferase
PIMT
Protein L-isoaspartyl methyltransferase
L-isoaspartyl protein carboxyl methyltransferase
EC 2.1.1.77
Protein-beta-aspartate methyltransferase
PIMT
Protein L-isoaspartyl methyltransferase
L-isoaspartyl protein carboxyl methyltransferase
Protein-L-isoaspartate O-methyltransferase beta-aspartate methyltransferase, putative
PIMT
EC 2.1.1.77
Protein-beta-aspartate methyltransferase
dPIMT
Protein L-isoaspartyl/D-aspartyl methyltransferase
L-isoaspartyl protein carboxyl methyltransferase
PIMT
EC 2.1.1.77
Protein-beta-aspartate methyltransferase
Protein L-isoaspartyl/D-aspartyl methyltransferase
L-isoaspartyl protein carboxyl methyltransferase
RefSeqNP_247140.1 (Protein)
NC_000909.1 (DNA/RNA sequence)
NP_579651.1 (Protein)
NC_003413.1 (DNA/RNA sequence)
XP_001348483.1 (Protein)
XM_001348447.1 (DNA/RNA sequence)
NP_536756.1 (Protein)
NM_080508.4 (DNA/RNA sequence)
NP_001238978.1 (Protein)
NM_001252049.1 (DNA/RNA sequence)
NP_001238982.1 (Protein)
NM_001252053.1 (DNA/RNA sequence)
PfamPF01135 (PCMT)
[Graphical view]
PF01135 (PCMT)
[Graphical view]
PF01135 (PCMT)
[Graphical view]
PF01135 (PCMT)
[Graphical view]
PF01135 (PCMT)
[Graphical view]


UniProtKB:Accession NumberQ57636Q8TZR3Q8ILD5Q27869P22061
Entry namePIMT_METJAPIMT_PYRFUQ8ILD5_PLAF7PIMT_DROMEPIMT_HUMAN
ActivityS-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester.S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester.
S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester.S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester.
Subunit
Monomer.
Monomer.Monomer.
Subcellular locationCytoplasm (By similarity).Cytoplasm (By similarity).
Cytoplasm (By similarity).Cytoplasm.
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

            
2yxeA00UnboundUnboundUnboundUnbound
2yxeB00UnboundUnboundUnboundUnbound
1jg1A00UnboundUnboundBound:SAHUnbound
1jg2A00UnboundUnboundAnalogue:ADNUnbound
1jg3A00UnboundBound:VAL-TYR-PRO-ASP-HIS-ALA(chain C)Analogue:ADNUnbound
1jg3B00UnboundBound:VAL-TYR-PRO-ASP-HIS-ALA(chain D)Analogue:ADNUnbound
1jg4A00Bound:SAMUnboundUnboundUnbound
2pbfA00UnboundUnboundBound:SAHUnbound
2pbfB00UnboundUnboundBound:SAHUnbound
1r18A00UnboundUnboundBound:SAHUnbound
1i1nA00UnboundUnboundBound:SAHUnbound
1kr5A00UnboundUnboundBound:SAHUnbound

Active-site residues
resource
literature [2], [7] & Swiss;Q57636, Q8TZR3, P22061, Q27869
pdbCatalytic residues
         
2yxeA00SER 61
2yxeB00SER 61
1jg1A00SER 75
1jg2A00SER 75
1jg3A00SER 75
1jg3B00SER 75
1jg4A00SER 75
2pbfA00SER 62
2pbfB00SER 62
1r18A00SER 60
1i1nA00SER 59
1kr5A00SER 59

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 a homologous enzyme counterpart with two domains (see S00823 in EzCatDB).
According to the literature [2] and [7], the reaction of this enzyme occurs as follows:
(1) Ser75 (PDB;1jg3) 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


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.