5cvd

From Proteopedia

(Difference between revisions)

Revision as of 04:32, 1 December 2015

Crystal structure of human NRMT1 in complex with alpha-N-dimethylated human CENP-A peptide

Structural highlights

5cvd is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	5cve
Activity:	Protein N-terminal methyltransferase, with EC number 2.1.1.244
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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] [CENPA_HUMAN] Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).^[4] ^[5]

Publication Abstract from PubMed

NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 A. NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases. Key substrate recognition and catalytic residues were identified by mutagenesis studies. Histone peptide profiling revealed that human NRMT1 is highly selective to human CENP-A and fruit fly H2B, which share a common "Xaa-Pro-Lys/Arg" motif. These results, along with a 1.5 A costructure of human NRMT1 bound to the fruit fly H2B peptide, underscore the importance of the NRMT1 recognition motif.

Molecular basis for histone N-terminal methylation by NRMT1.,Wu R, Yue Y, Zheng X, Li H Genes Dev. 2015 Nov 15;29(22):2337-42. doi: 10.1101/gad.270926.115. Epub 2015 Nov, 5. PMID:26543159^[6]

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
↑ Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Aug 25. PMID:20739937 doi:10.1038/nature09323
↑ Hu H, Liu Y, Wang M, Fang J, Huang H, Yang N, Li Y, Wang J, Yao X, Shi Y, Li G, Xu RM. Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP. Genes Dev. 2011 May 1;25(9):901-6. Epub 2011 Apr 8. PMID:21478274 doi:10.1101/gad.2045111
↑ Wu R, Yue Y, Zheng X, Li H. Molecular basis for histone N-terminal methylation by NRMT1. Genes Dev. 2015 Nov 15;29(22):2337-42. doi: 10.1101/gad.270926.115. Epub 2015 Nov, 5. PMID:26543159 doi:http://dx.doi.org/10.1101/gad.270926.115

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/5cvd"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of human NRMT1 in complex with alpha-N-dimethylated human CENP-A peptide==
+<StructureSection load='5cvd' size='340' side='right' caption='[[5cvd]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5cvd]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CVD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CVD FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMG:N,N-DIMETHYLGLYCINE'>DMG</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cve|5cve]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5cvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cvd OCA], [http://pdbe.org/5cvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cvd RCSB], [http://www.ebi.ac.uk/pdbsum/5cvd PDBsum]</span></td></tr>
+</table>
+== 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>  [[http://www.uniprot.org/uniprot/CENPA_HUMAN CENPA_HUMAN]] Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).<ref>PMID:20739937</ref> <ref>PMID:21478274</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 A. NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases. Key substrate recognition and catalytic residues were identified by mutagenesis studies. Histone peptide profiling revealed that human NRMT1 is highly selective to human CENP-A and fruit fly H2B, which share a common "Xaa-Pro-Lys/Arg" motif. These results, along with a 1.5 A costructure of human NRMT1 bound to the fruit fly H2B peptide, underscore the importance of the NRMT1 recognition motif.
-The entry 5cvd is ON HOLD
+Molecular basis for histone N-terminal methylation by NRMT1.,Wu R, Yue Y, Zheng X, Li H Genes Dev. 2015 Nov 15;29(22):2337-42. doi: 10.1101/gad.270926.115. Epub 2015 Nov, 5. PMID:26543159<ref>PMID:26543159</ref>
-Authors: Wu, R., Li, H.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of human NRMT1 in complex with alpha-N-dimethylated human CENP-A peptide
+<div class="pdbe-citations 5cvd" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Protein N-terminal methyltransferase]]
 [[Category: Li, H]]
 [[Category: Wu, R]]
+[[Category: Alpha-n-methyltransferase]]
+[[Category: Cenp-a]]
+[[Category: Histone methylation]]
+[[Category: Sam-mtase]]
+[[Category: Transferase-peptide complex]]

5cvd

From Proteopedia

Revision as of 04:32, 1 December 2015

Crystal structure of human NRMT1 in complex with alpha-N-dimethylated human CENP-A peptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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