6dtn

From Proteopedia

(Difference between revisions)

Current revision

The structure of NTMT1 in complex with compound DC100-1

Structural highlights

6dtn is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.475Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6dtn"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6dtn is ON HOLD
+==The structure of NTMT1 in complex with compound DC100-1==
+<StructureSection load='6dtn' size='340' side='right'caption='[[6dtn]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
+== Structural highlights ==
+<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.475&#8491;</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='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>
+</table>
+== Function ==
+[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;">
+== 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.
-Authors:
+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<ref>PMID:30883119</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6dtn" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Synthetic construct]]
+[[Category: Chen D]]
+[[Category: Huang R]]
+[[Category: Noinaj N]]

6dtn

From Proteopedia

Current revision

The structure of NTMT1 in complex with compound DC100-1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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