Search results for PCMT1

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Species

Types

Compartments

Reaction types

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Protein (1 results from a total of 1)

Identifier: R-HSA-5676580
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PCMT1: P22061

Interactor (1 results from a total of 1)

Identifier: P22061-2
Species: Homo sapiens
Primary external reference: UniProt: P22061-2

Reaction (2 results from a total of 2)

Identifier: R-HSA-5676966
Species: Homo sapiens
Compartment: cytosol
Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1, PIMT EC 2.1.1.77) transfers the methyl group from S-adenosyl-L-methionine (AdoMet) to the alpha side-chain carboxyl group of L-isoaspartyl and D-aspartatyl amino acids (Murray & Clarke 1986, Johnson et al. 1987, Galletti et al. 1988, Lowenson & Clarke 1992, The resulting methyl ester (MetAsp) undergoes spontaneous transformation to L-succinimide, which spontaneously hydrolyses to generates L-aspartyl residues or L-isoaspartyl residues. This repair process helps to maintain overall protein integrity. When PCMT1 is not present in cells, the abnormal aspartyl residues accumulate. Pcmt1 knockout mice exhibit fatal progressive epilepsy (Yamamoto et al. 1998).
Identifier: R-HSA-5687520
Species: Homo sapiens
Compartment: cytosol
The methyl ester produced by the action of PCMT1 on L-isoaspartyl and D-aspartatyl amino acids subsequently undergoes spontaneous transformation to L-succinimide, which further spontaneously hydrolyses to generates L-aspartyl residues or L-isoaspartyl residues (Murray & Clarke 1986, Johnson et al. 1987, Galletti et al. 1988, Lowenson & Clarke 1992). This repair process helps to maintain overall protein integrity. When PCMT1 is not present in cells, the abnormal aspartyl residues accumulate. Pcmt1 knockout mice exhibit fatal progressive epilepsy (Yamamoto et al. 1998).

Pathway (1 results from a total of 1)

Identifier: R-HSA-5676934
Species: Homo sapiens
Reactive oxygen species (ROS) such as H2O2, superoxide anions and hydroxyl radicals interact with molecules in the cell causing damage that impairs cellular functions. Although cells have mechanisms to destroy ROS and repair the damage caused by ROS, it is considered to be a major factor in age-related diseases and the ageing process (Zhang & Weissbach 2008, Kim et al. 2014). ROS-scavenging systems include enzymes such as peroxiredoxins, superoxide dismutases, catalases and glutathione peroxidases exist to minimise the potential damage.

ROS reactions can also cause specific modifications to amino acid side chains that result in structural changes to proteins/enzymes. Methionine (Met) and cysteine (Cys) can be oxidised by ROS to sulfoxide and further oxidised to sulfone derivatives. Both free Met and protein-based Met are readily oxidized to form methionine sulphoxide (MetO) (Brot & Weissbach 1991). Many proteins have been demonstrated to undergo such oxidation and as a consequence have altered function (Levine et al. 2000). Sulphoxide formation can be reversed by the action of the methionine sulphoxide reductase system (MSR) which catalyses the reduction of MetO to Met (Brot et al. 1981). This repair uses one ROS equivalent, so MSR proteins can act as catalytic antioxidants, removing ROS (Levine et al. 1996). Methionine oxidation results in a mixture of methionine (S)-S- and (R)-S-oxides of methionine, diastereomers which are reduced by MSRA and MSRB, respectively. MSRA can reduce both free and protein-based methionine-(S)-S-oxide, whereas MSRB is specific for protein-based methionine-(R)-S-oxide. Mammals typically have only one gene encoding MSRA, but at least three genes encoding MSRBs (Hansel et al. 2005). Although structurally distinct, MRSA and MRSB share a common three-step catalytic mechanism. In the first step, the MSR catalytic cysteine residue interacts with the MetO substrate, which leads to product release and formation of the sulfenic acid. In the second step, an intramolecular disulfide bridge is formed between the catalytic cysteine and the regenerating cysteine. In the final step, the disulfide bridge is reduced by an electron donor, the NADPH-dependent thioredoxin/TR system, leading to the regeneration of the MSR active site (Boschi-Muller et al. 2008).

Beta-linked isoaspartyl (isoAsp) peptide bonds can arise spontaneously via succinimide-linked deamidation of asparagine (Asn) or dehydration of aspartate (Asp). Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1, PIMT EC 2.1.1.77) transfers the methyl group from S-adenosyl-L-methionine (AdoMet) to the alpha side-chain carboxyl group of L-isoaspartyl and D-aspartatyl amino acids. The resulting methyl ester undergoes spontaneous transformation to L-succinimide, which spontaneously hydrolyses to generates L-aspartyl residues or L-isoaspartyl residues (Knorre et al. 2009). This repair process helps to maintain overall protein integrity.
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