PDBsum entry 1dl5

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
317 a.a. *
SAH ×2
_CD ×9
_CL ×10
Waters ×463
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Protein-l-isoaspartate o-methyltransferase
Structure: Protein-l-isoaspartate o-methyltransferase. Chain: a, b. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.80Å     R-factor:   0.182     R-free:   0.203
Authors: M.M.Skinner,J.M.Puvathingal,R.L.Walter,A.M.Friedman
Key ref:
M.M.Skinner et al. (2000). Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair. Structure, 8, 1189-1201. PubMed id: 11080641 DOI: 10.1016/S0969-2126(00)00522-0
08-Dec-99     Release date:   08-Dec-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q56308  (PIMT_THEMA) -  Protein-L-isoaspartate O-methyltransferase
317 a.a.
317 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-L-isoaspartate(D-aspartate) O-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L- homocysteine + protein L-isoaspartate alpha-methyl ester
+ protein L-isoaspartate
S-adenosyl-L- homocysteine
Bound ligand (Het Group name = SAH)
corresponds exactly
+ protein L-isoaspartate alpha-methyl ester
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     methylation   4 terms 
  Biochemical function     transferase activity     3 terms  


DOI no: 10.1016/S0969-2126(00)00522-0 Structure 8:1189-1201 (2000)
PubMed id: 11080641  
Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.
M.M.Skinner, J.M.Puvathingal, R.L.Walter, A.M.Friedman.
BACKGROUND: Formation of isoaspartyl residues is one of several processes that damage proteins as they age. Protein L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) is a conserved and nearly ubiquitous enzyme that catalyzes the repair of proteins damaged by isoaspartyl formation. RESULTS: We have determined the first structure of a PIMT from crystals of the T. maritima enzyme complexed to S-adenosyl-L-homocysteine (AdoHcy) and refined it to 1.8 A resolution. Although PIMT forms one structural unit, the protein can be divided functionally into three subdomains. The central subdomain closely resembles other S-adenosyl-L-methionine-dependent methyltransferases but bears a striking alteration of topological connectivity, which is not shared by any other member of this family. Rather than arranged as a mixed beta sheet with topology 6 upward arrow7 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow, the central sheet of PIMT is reorganized to 7 upward arrow6 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow. AdoHcy is largely buried between the N-terminal and central subdomains by a conserved and largely hydrophobic loop on one rim of the binding cleft, and a conserved Ser/Thr-rich beta strand on the other. The Ser/Thr-rich strand may provide hydrogen bonds for specific interactions with isoaspartyl substrates. The side chain of Ile-206, a conserved residue, crosses the cleft, restricting access to the donor methyl group to a deep well, the putative isoaspartyl methyl acceptor site. CONCLUSIONS: The structure of PIMT reveals a unique modification of the methyltransferase fold along with a site for specific recognition of isoaspartyl substrates. The sequence conservation among PIMTs suggests that the current structure should prove a reliable model for understanding the repair of isoaspartyl damage in all organisms.
  Selected figure(s)  
Figure 2.
Figure 2. Ca Backbone and Secondary Structure Elements of T. maritima PIMT(a) Stereo diagram of the Ca backbone. The N and C termini and every tenth residue are marked. AdoHcy is shown as a stick model with the Sd atom, the site of methyl group transfer, drawn as a white sphere. The approximate locations of the East and West Rims are indicated.(b) Stereo diagram of secondary structure elements. For clarity not all secondary structure elements are labeled. AdoHcy is drawn as in (a). This figure was prepared using MOLSCRIPT [59]

  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1189-1201) copyright 2000.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19801578 K.Rutherford, and V.Daggett (2009).
The V119I polymorphism in protein L-isoaspartate O-methyltransferase alters the substrate-binding interface.
  Protein Eng Des Sel, 22, 713-721.  
18057781 T.Furuchi, and H.Homma (2007).
[Role of isomerized protein repair enzyme, PIMT, in cellular functions]
  Yakugaku Zasshi, 127, 1927-1936.  
16575568 H.Zhu, R.J.Pan, T.W.Wang, Y.L.Shen, and D.Z.Wei (2006).
Functional solubilization of aggregation-prone TRAIL protein facilitated by coexpressing with protein isoaspartate methyltranferase.
  Appl Microbiol Biotechnol, 72, 1033-1038.  
15169774 Y.Tanaka, K.Tsumoto, Y.Yasutake, M.Umetsu, M.Yao, H.Fukada, I.Tanaka, and I.Kumagai (2004).
How oligomerization contributes to the thermostability of an archaeon protein. Protein L-isoaspartyl-O-methyltransferase from Sulfolobus tokodaii.
  J Biol Chem, 279, 32957-32967.
PDB code: 1vbf
14596598 E.J.Bennett, J.Bjerregaard, J.E.Knapp, D.A.Chavous, A.M.Friedman, W.E.Royer, and C.M.O'Connor (2003).
Catalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis.
  Biochemistry, 42, 12844-12853.
PDB code: 1r18
12826405 H.L.Schubert, R.M.Blumenthal, and X.Cheng (2003).
Many paths to methyltransfer: a chronicle of convergence.
  Trends Biochem Sci, 28, 329-335.  
14527954 J.Kindrachuk, J.Parent, G.F.Davies, M.Dinsmore, S.Attah-Poku, and S.Napper (2003).
Overexpression of L-isoaspartate O-methyltransferase in Escherichia coli increases heat shock survival by a mechanism independent of methyltransferase activity.
  J Biol Chem, 278, 50880-50886.  
12596263 K.Lim, H.Zhang, A.Tempczyk, W.Krajewski, N.Bonander, J.Toedt, A.Howard, E.Eisenstein, and O.Herzberg (2003).
Structure of the YibK methyltransferase from Haemophilus influenzae (HI0766): a cofactor bound at a site formed by a knot.
  Proteins, 51, 56-67.
PDB codes: 1j85 1mxi
12726775 S.Clarke (2003).
Aging as war between chemical and biochemical processes: protein methylation and the recognition of age-damaged proteins for repair.
  Ageing Res Rev, 2, 263-285.  
11847284 C.D.Smith, M.Carson, A.M.Friedman, M.M.Skinner, L.Delucas, L.Chantalat, L.Weise, T.Shirasawa, and D.Chattopadhyay (2002).
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.
  Protein Sci, 11, 625-635.
PDB code: 1i1n
11792715 C.Ryttersgaard, S.C.Griffith, M.R.Sawaya, D.C.MacLaren, S.Clarke, and T.O.Yeates (2002).
Crystal structure of human L-isoaspartyl methyltransferase.
  J Biol Chem, 277, 10642-10646.
PDB code: 1kr5
12377117 G.Michel, V.Sauvé, R.Larocque, Y.Li, A.Matte, and M.Cygler (2002).
The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot.
  Structure, 10, 1303-1315.
PDB code: 1gz0
11742076 D.A.Chavous, F.R.Jackson, and C.M.O'Connor (2001).
Extension of the Drosophila lifespan by overexpression of a protein repair methyltransferase.
  Proc Natl Acad Sci U S A, 98, 14814-14818.  
11557810 X.Cheng, and R.J.Roberts (2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
  Nucleic Acids Res, 29, 3784-3795.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.