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| | <StructureSection load='6dtn' size='340' side='right'caption='[[6dtn]], [[Resolution|resolution]] 1.48Å' scene=''> | | <StructureSection load='6dtn' size='340' side='right'caption='[[6dtn]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dtn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DTN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dtn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DTN FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6D6:5-{[(3S)-3-AMINO-3-CARBOXYPROPYL](3-AMINOPROPYL)AMINO}-5-DEOXYADENOSINE'>6D6</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.475Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NTMT1, C9orf32, METTL11A, NRMT, NRMT1, AD-003 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6D6:5-{[(3S)-3-AMINO-3-CARBOXYPROPYL](3-AMINOPROPYL)AMINO}-5-DEOXYADENOSINE'>6D6</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_N-terminal_methyltransferase Protein N-terminal methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.244 2.1.1.244] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dtn OCA], [https://pdbe.org/6dtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dtn RCSB], [https://www.ebi.ac.uk/pdbsum/6dtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dtn ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dtn OCA], [http://pdbe.org/6dtn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dtn RCSB], [http://www.ebi.ac.uk/pdbsum/6dtn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dtn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NTM1A_HUMAN NTM1A_HUMAN]] Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by METTL11B-mediated monomethylation. Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1.<ref>PMID:20481588</ref> <ref>PMID:20668449</ref> <ref>PMID:24090352</ref> | + | [https://www.uniprot.org/uniprot/NTM1A_HUMAN NTM1A_HUMAN] Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by METTL11B-mediated monomethylation. Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1.<ref>PMID:20481588</ref> <ref>PMID:20668449</ref> <ref>PMID:24090352</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein N-terminal methyltransferase]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Chen, D]] | + | [[Category: Chen D]] |
| - | [[Category: Huang, R]] | + | [[Category: Huang R]] |
| - | [[Category: Noinaj, N]] | + | [[Category: Noinaj N]] |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Inhibitor complex]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
NTM1A_HUMAN Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by METTL11B-mediated monomethylation. Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1.[1] [2] [3]
Publication Abstract from PubMed
Protein N-terminal methyltransferase 1 (NTMT1) plays an important role in regulating mitosis and DNA repair. Here, we describe the discovery of a potent NTMT1 bisubstrate inhibitor 4 (IC50 = 35 +/- 2 nM) that exhibits greater than 100-fold selectivity against a panel of methyltransferases. We also report the first crystal structure of NTMT1 in complex with an inhibitor, which revealed that 4 occupies substrate and cofactor binding sites of NTMT1.
Discovery of Bisubstrate Inhibitors for Protein N-Terminal Methyltransferase 1.,Chen D, Dong G, Noinaj N, Huang R J Med Chem. 2019 Mar 27. doi: 10.1021/acs.jmedchem.9b00206. PMID:30883119[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Webb KJ, Lipson RS, Al-Hadid Q, Whitelegge JP, Clarke SG. Identification of protein N-terminal methyltransferases in yeast and humans. Biochemistry. 2010 Jun 29;49(25):5225-35. doi: 10.1021/bi100428x. PMID:20481588 doi:http://dx.doi.org/10.1021/bi100428x
- ↑ Tooley CE, Petkowski JJ, Muratore-Schroeder TL, Balsbaugh JL, Shabanowitz J, Sabat M, Minor W, Hunt DF, Macara IG. NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature. 2010 Aug 26;466(7310):1125-8. doi: 10.1038/nature09343. PMID:20668449 doi:http://dx.doi.org/10.1038/nature09343
- ↑ Petkowski JJ, Bonsignore LA, Tooley JG, Wilkey DW, Merchant ML, Macara IG, Schaner Tooley CE. NRMT2 is an N-terminal monomethylase that primes for its homologue NRMT1. Biochem J. 2013 Dec 15;456(3):453-62. doi: 10.1042/BJ20131163. PMID:24090352 doi:http://dx.doi.org/10.1042/BJ20131163
- ↑ Chen D, Dong G, Noinaj N, Huang R. Discovery of Bisubstrate Inhibitors for Protein N-Terminal Methyltransferase 1. J Med Chem. 2019 Mar 27. doi: 10.1021/acs.jmedchem.9b00206. PMID:30883119 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00206
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