PDBsum entry 1jg3

Transferase

PDB id: 1jg3

Contents

Protein chains

215 a.a. *

Ligands

VAL-TYR-PRO-IAS-HIS-ALA ×2

ADN ×2

Metals

_CL ×2

_NA ×2

Waters ×210

* Residue conservation analysis

PDB id:

1jg3

Name:

Transferase

Title:

Crystal structure of l-isoaspartyl (d-aspartyl) o-methyltransferase with adenosine & vyp(isp)ha substrate

Structure:

Protein-l-isoaspartate o-methyltransferase. Chain: a, b. Synonym: protein-beta-aspartate methyltransferase. Pimt. Protein l- isoaspartyl methyltransferase. L-isoaspartyl protein carboxyl methyltransferase. Engineered: yes. Vyp(l-iso-asp)ha. Chain: c, d. Engineered: yes.

Source:

Pyrococcus furiosus. Organism_taxid: 2261. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.204 R-free: 0.233

Authors:

S.C.Griffith,M.R.Sawaya,D.Boutz,N.Thapar,J.Katz,S.Clarke,T.O.Yeates

Key ref:

S.C.Griffith et al. (2001). Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate. J Mol Biol, 313, 1103-1116. PubMed id: 11700066 DOI: 10.1006/jmbi.2001.5095

Date:

22-Jun-01 Release date: 16-Nov-01

Protein chains

Q8TZR3  (PIMT_PYRFU) -  Protein-L-isoaspartate O-methyltransferase from Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)

Seq: 219 a.a.

Struc: 215 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.1.1.77 - protein-L-isoaspartate(D-aspartate) O-methyltransferase.
• Reaction: [protein]-L-isoaspartate + S-adenosyl-L-methionine = [protein]-L- isoaspartate alpha-methyl ester + S-adenosyl-L-homocysteine

[protein]-L-isoaspartate (Bound ligand (Het Group name = ADN) matches with 64.29% similarity) + S-adenosyl-L-methionine (Bound ligand (Het Group name = IAS) matches with 61.54% similarity) = [protein]-L- isoaspartate alpha-methyl ester + S-adenosyl-L-homocysteine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1006/jmbi.2001.5095

J Mol Biol 313:1103-1116 (2001)

PubMed id: 11700066

Crystal structure of a protein repair methyltransferase from Pyrococcus furiosus with its L-isoaspartyl peptide substrate.

S.C.Griffith, M.R.Sawaya, D.R.Boutz, N.Thapar, J.E.Katz, S.Clarke, T.O.Yeates.

ABSTRACT

Protein L-isoaspartyl (D-aspartyl) methyltransferases (EC 2.1.1.77) are found in almost all organisms. These enzymes catalyze the S-adenosylmethionine (AdoMet)-dependent methylation of isomerized and racemized aspartyl residues in age-damaged proteins as part of an essential protein repair process. Here, we report crystal structures of the repair methyltransferase at resolutions up to 1.2 A from the hyperthermophilic archaeon Pyrococcus furiosus. Refined structures include binary complexes with the active cofactor AdoMet, its reaction product S-adenosylhomocysteine (AdoHcy), and adenosine. The enzyme places the methyl-donating cofactor in a deep, electrostatically negative pocket that is shielded from solvent. Across the multiple crystal structures visualized, the presence or absence of the methyl group on the cofactor correlates with a significant conformational change in the enzyme in a loop bordering the active site, suggesting a role for motion in catalysis or cofactor exchange. We also report the structure of a ternary complex of the enzyme with adenosine and the methyl-accepting polypeptide substrate VYP(L-isoAsp)HA at 2.1 A. The substrate binds in a narrow active site cleft with three of its residues in an extended conformation, suggesting that damaged proteins may be locally denatured during the repair process in cells. Manual and computer-based docking studies on different isomers help explain how the enzyme uses steric effects to make the critical distinction between normal L-aspartyl and age-damaged L-isoaspartyl and D-aspartyl residues.

Selected figure(s)

Figure 3.
Figure 3. Stereo view of a ribbon diagram of the P. furiosus Image -isoaspartyl methyltransferase. The structure shown is that of the ternary complex with adenosine in stick form and the peptide VYP( Image -isoAsp)HA in ball-and-stick form. The secondary structures are labeled as in Figure 2. This Figure was made with SETOR [62].

Figure 5.
Figure 5. A protein conformational difference between the AdoMet (red) and AdoHcy (green) complexes of the P. furiosus isoaspartyl methyltransferase. The largest coordinate differences are over 10 Å. This Figure was produced with SETOR[62].

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 313, 1103-1116) copyright 2001.

Figures were selected by an automated process.