2bqz
From Proteopedia
(New page: 200px<br /><applet load="2bqz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bqz, resolution 1.50Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:2bqz.gif|left|200px]]<br /><applet load="2bqz" size=" | + | [[Image:2bqz.gif|left|200px]]<br /><applet load="2bqz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2bqz, resolution 1.50Å" /> | caption="2bqz, resolution 1.50Å" /> | ||
'''CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF THE HUMAN HISTONE METHYLTRANSFERASE PR-SET7 (ALSO KNOWN AS SET8)'''<br /> | '''CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF THE HUMAN HISTONE METHYLTRANSFERASE PR-SET7 (ALSO KNOWN AS SET8)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Methylation of lysine residues of histones is an important epigenetic mark | + | Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific. |
==About this Structure== | ==About this Structure== | ||
| - | 2BQZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SAH as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] Full crystallographic information is available from [http:// | + | 2BQZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BQZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Frenkiel, T | + | [[Category: Frenkiel, T A.]] |
| - | [[Category: Gamblin, S | + | [[Category: Gamblin, S J.]] |
[[Category: Jing, C.]] | [[Category: Jing, C.]] | ||
[[Category: Kelly, G.]] | [[Category: Kelly, G.]] | ||
| - | [[Category: Martin, S | + | [[Category: Martin, S R.]] |
| - | [[Category: Muskett, F | + | [[Category: Muskett, F W.]] |
[[Category: Reinberg, D.]] | [[Category: Reinberg, D.]] | ||
[[Category: Sarma, K.]] | [[Category: Sarma, K.]] | ||
| - | [[Category: Walker, P | + | [[Category: Walker, P A.]] |
| - | [[Category: Wilson, J | + | [[Category: Wilson, J R.]] |
[[Category: Xiao, B.]] | [[Category: Xiao, B.]] | ||
[[Category: SAH]] | [[Category: SAH]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:40:42 2008'' |
Revision as of 14:40, 21 February 2008
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CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF THE HUMAN HISTONE METHYLTRANSFERASE PR-SET7 (ALSO KNOWN AS SET8)
Overview
Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific.
About this Structure
2BQZ is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Full crystallographic information is available from OCA.
Reference
Specificity and mechanism of the histone methyltransferase Pr-Set7., Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ, Wilson JR, Genes Dev. 2005 Jun 15;19(12):1444-54. Epub 2005 Jun 2. PMID:15933069
Page seeded by OCA on Thu Feb 21 16:40:42 2008
Categories: Histone-lysine N-methyltransferase | Homo sapiens | Protein complex | Frenkiel, T A. | Gamblin, S J. | Jing, C. | Kelly, G. | Martin, S R. | Muskett, F W. | Reinberg, D. | Sarma, K. | Walker, P A. | Wilson, J R. | Xiao, B. | SAH | Histone h4 methyltransfersae | Lysine methyltransferase | Set domain | Transferase
