1peg
From Proteopedia
(New page: 200px<br /><applet load="1peg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1peg, resolution 2.59Å" /> '''Structural basis for...) |
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| - | [[Image:1peg.gif|left|200px]]<br /><applet load="1peg" size=" | + | [[Image:1peg.gif|left|200px]]<br /><applet load="1peg" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1peg, resolution 2.59Å" /> | caption="1peg, resolution 2.59Å" /> | ||
'''Structural basis for the product specificity of histone lysine methyltransferases'''<br /> | '''Structural basis for the product specificity of histone lysine methyltransferases'''<br /> | ||
==Overview== | ==Overview== | ||
| - | DIM-5 is a SUV39-type histone H3 Lys9 methyltransferase that is essential | + | DIM-5 is a SUV39-type histone H3 Lys9 methyltransferase that is essential for DNA methylation in N. crassa. We report the structure of a ternary complex including DIM-5, S-adenosyl-L-homocysteine, and a substrate H3 peptide. The histone tail inserts as a parallel strand between two DIM-5 strands, completing a hybrid sheet. Three post-SET cysteines coordinate a zinc atom together with Cys242 from the SET signature motif (NHXCXPN) near the active site. Consequently, a narrow channel is formed to accommodate the target Lys9 side chain. The sulfur atom of S-adenosyl-L-homocysteine, where the transferable methyl group is to be attached in S-adenosyl-L-methionine, lies at the opposite end of the channel, approximately 4 A away from the target Lys9 nitrogen. Structural comparison of the active sites of DIM-5, an H3 Lys9 trimethyltransferase, and SET7/9, an H3 Lys4 monomethyltransferase, allowed us to design substitutions in both enzymes that profoundly alter their product specificities without affecting their catalytic activities. |
==About this Structure== | ==About this Structure== | ||
| - | 1PEG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Neurospora_crassa Neurospora crassa] with ZN and SAH as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1PEG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Neurospora_crassa Neurospora crassa] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1PEG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Cheng, X.]] | [[Category: Cheng, X.]] | ||
| - | [[Category: Horton, J | + | [[Category: Horton, J R.]] |
| - | [[Category: Khan, S | + | [[Category: Khan, S I.]] |
| - | [[Category: Selker, E | + | [[Category: Selker, E U.]] |
[[Category: Tamaru, H.]] | [[Category: Tamaru, H.]] | ||
[[Category: Yang, Z.]] | [[Category: Yang, Z.]] | ||
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[[Category: ternary structure of dim-5]] | [[Category: ternary structure of dim-5]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:28:04 2008'' |
Revision as of 12:28, 21 February 2008
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Structural basis for the product specificity of histone lysine methyltransferases
Overview
DIM-5 is a SUV39-type histone H3 Lys9 methyltransferase that is essential for DNA methylation in N. crassa. We report the structure of a ternary complex including DIM-5, S-adenosyl-L-homocysteine, and a substrate H3 peptide. The histone tail inserts as a parallel strand between two DIM-5 strands, completing a hybrid sheet. Three post-SET cysteines coordinate a zinc atom together with Cys242 from the SET signature motif (NHXCXPN) near the active site. Consequently, a narrow channel is formed to accommodate the target Lys9 side chain. The sulfur atom of S-adenosyl-L-homocysteine, where the transferable methyl group is to be attached in S-adenosyl-L-methionine, lies at the opposite end of the channel, approximately 4 A away from the target Lys9 nitrogen. Structural comparison of the active sites of DIM-5, an H3 Lys9 trimethyltransferase, and SET7/9, an H3 Lys4 monomethyltransferase, allowed us to design substitutions in both enzymes that profoundly alter their product specificities without affecting their catalytic activities.
About this Structure
1PEG is a Protein complex structure of sequences from Neurospora crassa with and as ligands. Active as Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Full crystallographic information is available from OCA.
Reference
Structural basis for the product specificity of histone lysine methyltransferases., Zhang X, Yang Z, Khan SI, Horton JR, Tamaru H, Selker EU, Cheng X, Mol Cell. 2003 Jul;12(1):177-85. PMID:12887903
Page seeded by OCA on Thu Feb 21 14:28:04 2008
Categories: Histone-lysine N-methyltransferase | Neurospora crassa | Protein complex | Cheng, X. | Horton, J R. | Khan, S I. | Selker, E U. | Tamaru, H. | Yang, Z. | Zhang, X. | SAH | ZN | A hybrid beta sheet formed by dim-5 and h3 tail | A suv39-type histone-h3 lys-9 methyltransferase | Post-set zinc-binding site | Pre-set triangular zn3cys9 zinc cluster | Set domain protein forms a knot-like substructure | Ternary structure of dim-5
