1r18
From Proteopedia
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Drosophila protein isoaspartyl methyltransferase with S-adenosyl-L-homocysteine
Overview
Protein L-isoaspartyl methyltransferases (PIMT; EC 2.1.1.77) catalyze the, S-adenosylmethionine-dependent methylation of L-isoaspartyl residues that, arise spontaneously in proteins with age, thereby initiating a repair, process that restores the normal backbone configuration to the damaged, polypeptide. In Drosophila melanogaster, overexpression of PIMT in, transgenic flies extends the normal life span, suggesting that protein, damage can be a limiting factor in longevity. To understand structural, features of the Drosophila PIMT (dPIMT) important for catalysis, the, crystal structure of dPIMT was determined at a resolution of 2.2 A, and, site-directed mutagenesis was used to identify the role of Ser-60 in, catalysis. The core structure of dPIMT is similar to the modified, nucleotide-binding fold observed in PIMTs from extreme thermophiles and, humans. A striking difference of the dPIMT structure is the rotation of, the C-terminal residues by 90 degrees relative to the homologous, structures. Effectively, this displacement generates a more open, conformation that allows greater solvent access to S-adenosylhomocysteine, which is almost completely buried in other PIMT structures. The enzyme may, alternate between the open conformation found for dPIMT and the more, closed conformations described for other PIMTs during its catalytic cycle, thereby allowing the exchange of substrates and products. Catalysis by, dPIMT requires the side chain of the conserved, active site residue, Ser-60, since substitution of this residue with Thr, Gln, or Ala reduces, or abolishes the methylation of both protein and isoaspartyl peptide, substrates.
About this Structure
1R18 is a Single protein structure of sequence from Drosophila melanogaster with SAH as ligand. Active as Protein-L-isoaspartate(D-aspartate) O-methyltransferase, with EC number 2.1.1.77 Full crystallographic information is available from OCA.
Reference
Catalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis., Bennett EJ, Bjerregaard J, Knapp JE, Chavous DA, Friedman AM, Royer WE Jr, O'Connor CM, Biochemistry. 2003 Nov 11;42(44):12844-53. PMID:14596598
Page seeded by OCA on Wed Nov 21 01:11:24 2007
Categories: Drosophila melanogaster | Protein-L-isoaspartate(D-aspartate) O-methyltransferase | Single protein | Bennett, E.J. | Bjerregaard, J. | Chavous, D.A. | Connor, C.M.O. | Friedman, A.M. | Jr., W.E.Royer. | Knapp, J.E. | SAH | Isomerization | Methyltransferase | Protein repair | S-adenosyl homocysteine
