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| ==Crystal structure of human alpha N-terminal protein methyltransferase 1B== | | ==Crystal structure of human alpha N-terminal protein methyltransferase 1B== |
| <StructureSection load='5ubb' size='340' side='right' caption='[[5ubb]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5ubb' size='340' side='right'caption='[[5ubb]], [[Resolution|resolution]] 2.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[5ubb]] is a 1 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=5UBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UBB FirstGlance]. <br> | | <table><tr><td colspan='2'>[[5ubb]] is a 1 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=5UBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UBB FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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]] 2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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_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'>[https://proteopedia.org/fgij/fg.htm?mol=5ubb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ubb OCA], [https://pdbe.org/5ubb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ubb RCSB], [https://www.ebi.ac.uk/pdbsum/5ubb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ubb 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=5ubb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ubb OCA], [http://pdbe.org/5ubb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ubb RCSB], [http://www.ebi.ac.uk/pdbsum/5ubb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ubb 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;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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<ref>PMID:30417120</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 5ubb" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __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, A]] | | [[Category: Dong A]] |
| [[Category: Dong, C]] | | [[Category: Dong C]] |
| [[Category: Edwards, A M]] | | [[Category: Edwards AM]] |
| [[Category: Min, J]] | | [[Category: Min J]] |
| [[Category: Structural genomic]]
| | [[Category: Tempel W]] |
| [[Category: Tempel, W]] | | [[Category: Zhu L]] |
| [[Category: Zhu, L]] | |
| [[Category: Methyl transferase]]
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| [[Category: Sgc]]
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| [[Category: Transferase]]
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