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Literature summary for 2.1.1.244 extracted from
- Molecular basis for histone N-terminal methylation by NRMT1 (2015), Genes Dev., 29, 2337-2342 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli | Homo sapiens |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| purified recombinant NRMT1 bound to CENP-A peptide and to the fruit fly H2B peptide in presence of S-adenosyl-L-homocysteine, vapor diffusion method, X-ray diffraction structure determination and analysis at 1.3 A and 1.5 A resolution, respectively | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| D180N | site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type | Homo sapiens |
| D212N | site-directed mutagenesis, the mutant shows reduced activity compared to wild-type | Homo sapiens |
| E213A | site-directed mutagenesis, the mutant shows 15% reduced activity compared to wild-type | Homo sapiens |
| N168A | site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type | Homo sapiens |
| W136L | site-directed mutagenesis, the mutant shows 92% reduced activity compared to wild-type | Homo sapiens |
| Y19A | site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type | Homo sapiens |
| Y19F | site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type | Homo sapiens |
| Y215A | site-directed mutagenesis, the mutant shows reduced activity compared to wild-type | Homo sapiens |
| Y215I | site-directed mutagenesis, the mutant shows reduced activity compared to wild-type | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| S-adenosyl-L-methionine + N-terminal-CENP-A | Homo sapiens | human CENP-A histone | S-adenosyl-L-homocysteine + ? | - |
? |  |
| S-adenosyl-L-methionine + N-terminal-histone 2B | Homo sapiens | fruit fly histone 2B | S-adenosyl-L-homocysteine + ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q9BV86 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2 S-adenosyl-L-methionine + N-terminal-histone 2B | dimethylation of fruit fly histone 2B by NTMT1 over an N-terminal sequence of 1PPKTSGKAA9 | Homo sapiens | 2 S-adenosyl-L-homocysteine + ? | - |
? | |
| 3 S-adenosyl-L-methionine + N-terminal-CENP-A | human CENP-A histone, molecular details for CENP-A recognition by NRMT1. State-specific trimethylation of CENP-A by NRMT1 | Homo sapiens | 3 S-adenosyl-L-homocysteine + ? | - |
? | |
| additional information | histone peptide profiling reveals that human NRMT1is highly selective to human CENP-A and fruit fly H2B, which share a common Xaa-Pro-Lys/Arg motif | Homo sapiens | ? | - |
- |
|
| S-adenosyl-L-methionine + N-terminal-CENP-A | human CENP-A histone | Homo sapiens | S-adenosyl-L-homocysteine + ? | - |
? | |
| S-adenosyl-L-methionine + N-terminal-histone 2B | fruit fly histone 2B | Homo sapiens | S-adenosyl-L-homocysteine + ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| N-terminal methyltransferase | - |
Homo sapiens |
| NRMT1 | - |
Homo sapiens |
Temperature Stability [°C]
| Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|
| additional information | - |
all of the mutant peptides that lost methylation capacity display no or negligible stabilization effect of NRMT1, suggesting loss of peptide binding due to residue substitution. In contrast, G1A and G1P CENP-A mutants stabilize NRMT1 by 1.5°C and 5.5°C compared with that of the NRMT1-SAH binary complex, consistent with their retained methylation capacity | Homo sapiens |
| 45 | - |
SAH-saturated NRMT1 displays a melting temperature (Tm) of 45°C, and the incubation with CENP-A (1-9) peptide further elevates the Tm by 3°C | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| S-adenosyl-L-methionine | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | enzymatic functional conservation of NRMT1 across species, evolutionary conservation of histone alpha-N-modification. Coevolution of NRMT1 recognition motifs in RCC1, CENP-A, and CENP-B, in which sequences 1SPKRIA6 of RCC1, 1GPRRRS6 of CENP-A, and 1GPKRRQ6 of CENP-B co-occur in mammals but are all missing in lower organisms. In contrast, the NRMT1 recognition motif of histone H2B is conserved from ciliates to insects but is lost in mammals. Remarkably, yeast and chicken orthologues of the above proteins do not harbor an NRMT1 recognition motif, suggesting that NRMT1 may exert its cellular function in these organisms through other protein substrates | Homo sapiens |
| additional information | ternary structures of human NRMT1 bound to alpha-N-methylated peptides of human histone CENP-A or fruit fly histone H2B in the presence of SAH, NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases, key substrate recognition and catalytic residues, NTMT1 structure-function analysis, overview. NRMT1 harbors a canonical SAM-dependent methyltransferase (SAM-MTase) core fold consisting of a seven-stranded beta-sheet (beta1-beta7) sandwiched by five flanking alpha-helices. Active site structure and catalytic mechanism analysis | Homo sapiens |
| physiological function | NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates | Homo sapiens |
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