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| | ==Crystal structure of a methyltransferase== | | ==Crystal structure of a methyltransferase== |
| - | <StructureSection load='6dub' size='340' side='right' caption='[[6dub]], [[Resolution|resolution]] 1.20Å' scene=''> | + | <StructureSection load='6dub' size='340' side='right'caption='[[6dub]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dub]] is a 4 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=6DUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DUB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dub]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DUB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 1.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5JP:N-METHYL-L-SERINE'>5JP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5JP:N-METHYL-L-SERINE'>5JP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METTL11B, C1orf184, NRMT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6dub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dub OCA], [https://pdbe.org/6dub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dub RCSB], [https://www.ebi.ac.uk/pdbsum/6dub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dub ProSAT]</span></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_monomethyltransferase Protein N-terminal monomethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.299 2.1.1.299] </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=6dub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dub OCA], [http://pdbe.org/6dub PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dub RCSB], [http://www.ebi.ac.uk/pdbsum/6dub PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dub ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NTM1B_HUMAN NTM1B_HUMAN]] 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 monomethylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif. May activate NTMT1 by priming its substrates for trimethylation.<ref>PMID:24090352</ref> | + | [https://www.uniprot.org/uniprot/NTM1B_HUMAN NTM1B_HUMAN] 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 monomethylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif. May activate NTMT1 by priming its substrates for trimethylation.<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: Protein N-terminal monomethyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Dong, C]] | + | [[Category: Dong C]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Li, Y]] | + | [[Category: Li Y]] |
| - | [[Category: Min, J]] | + | [[Category: Min J]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Tempel W]] |
| - | [[Category: Tempel, W]] | + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
NTM1B_HUMAN 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 monomethylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif. May activate NTMT1 by priming its substrates for trimethylation.[1]
Publication Abstract from PubMed
alpha-N-terminal methylation of proteins is an important post-translational modification that is catalyzed by two different N-terminal methyltransferases, namely NTMT1 and NTMT2. Previous studies have suggested that NTMT1 is a tri-methyltransferase, whereas NTMT2 is a mono-methyltransferase. Here, we report the first crystal structures, to our knowledge, of NTMT2 in binary complex with S-adenosyl-L-methionine as well as in ternary complex with S-adenosyl-L-homocysteine and a substrate peptide. Our structural observations combined with biochemical studies reveal that NTMT2 is also able to di-/tri-methylate the GPKRIA peptide and di-methylate the PPKRIA peptide, otherwise it is predominantly a mono-methyltransferase. The residue N89 of NTMT2 serves as a gatekeeper residue that regulates the binding of unmethylated versus monomethylated substrate peptide. Structural comparison of NTMT1 and NTMT2 prompts us to design a N89G mutant of NTMT2 that can profoundly alter its catalytic activities and product specificities.
An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2.,Dong C, Dong G, Li L, Zhu L, Tempel W, Liu Y, Huang R, Min J Commun Biol. 2018 Nov 2;1:183. doi: 10.1038/s42003-018-0196-2. eCollection 2018. PMID:30417120[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Dong C, Dong G, Li L, Zhu L, Tempel W, Liu Y, Huang R, Min J. An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2. Commun Biol. 2018 Nov 2;1:183. doi: 10.1038/s42003-018-0196-2. eCollection 2018. PMID:30417120 doi:http://dx.doi.org/10.1038/s42003-018-0196-2
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