1qsn
From Proteopedia
(New page: 200px<br /><applet load="1qsn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qsn, resolution 2.20Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1qsn.gif|left|200px]]<br /><applet load="1qsn" size=" | + | [[Image:1qsn.gif|left|200px]]<br /><applet load="1qsn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qsn, resolution 2.20Å" /> | caption="1qsn, resolution 2.20Å" /> | ||
'''CRYSTAL STRUCTURE OF TETRAHYMENA GCN5 WITH BOUND COENZYME A AND HISTONE H3 PEPTIDE'''<br /> | '''CRYSTAL STRUCTURE OF TETRAHYMENA GCN5 WITH BOUND COENZYME A AND HISTONE H3 PEPTIDE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Gene activation is a highly regulated process that requires the | + | Gene activation is a highly regulated process that requires the coordinated action of proteins to relieve chromatin repression and to promote transcriptional activation. Nuclear histone acetyltransferase (HAT) enzymes provide a mechanistic link between chromatin destabilization and gene activation by acetylating the epsilon-amino group of specific lysine residues within the aminoterminal tails of core histones to facilitate access to DNA by transcriptional activators. Here we report the high-resolution crystal structure of the HAT domain of Tetrahymena GCN5 (tGCN5) bound with both its physiologically relevant ligands, coenzyme A (CoA) and a histone H3 peptide, and the structures of nascent tGCN5 and a tGCN5/acetyl-CoA complex. Our structural data reveal histone-binding specificity for a random-coil structure containing a G-K-X-P recognition sequence, and show that CoA is essential for reorienting the enzyme for histone binding. Catalysis appears to involve water-mediated proton extraction from the substrate lysine by a glutamic acid general base and a backbone amide that stabilizes the transition-state reaction intermediate. Comparison with related N-acetyltransferases indicates a conserved structural framework for CoA binding and catalysis, and structural variability in regions associated with substrate-specific binding. |
==About this Structure== | ==About this Structure== | ||
| - | 1QSN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [http://en.wikipedia.org/wiki/Tetrahymena_thermophila Tetrahymena thermophila] with COA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1QSN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [http://en.wikipedia.org/wiki/Tetrahymena_thermophila Tetrahymena thermophila] with <scene name='pdbligand=COA:'>COA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QSN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Tetrahymena thermophila]] | [[Category: Tetrahymena thermophila]] | ||
| - | [[Category: Allis, C | + | [[Category: Allis, C David.]] |
| - | [[Category: Berger, S | + | [[Category: Berger, S L.]] |
[[Category: Li, X.]] | [[Category: Li, X.]] | ||
[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
[[Category: Mo, Y.]] | [[Category: Mo, Y.]] | ||
| - | [[Category: Rojas, J | + | [[Category: Rojas, J R.]] |
| - | [[Category: Trievel, R | + | [[Category: Trievel, R C.]] |
[[Category: Zhou, J.]] | [[Category: Zhou, J.]] | ||
[[Category: COA]] | [[Category: COA]] | ||
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[[Category: ternary complex]] | [[Category: ternary complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:43:14 2008'' |
Revision as of 12:43, 21 February 2008
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CRYSTAL STRUCTURE OF TETRAHYMENA GCN5 WITH BOUND COENZYME A AND HISTONE H3 PEPTIDE
Overview
Gene activation is a highly regulated process that requires the coordinated action of proteins to relieve chromatin repression and to promote transcriptional activation. Nuclear histone acetyltransferase (HAT) enzymes provide a mechanistic link between chromatin destabilization and gene activation by acetylating the epsilon-amino group of specific lysine residues within the aminoterminal tails of core histones to facilitate access to DNA by transcriptional activators. Here we report the high-resolution crystal structure of the HAT domain of Tetrahymena GCN5 (tGCN5) bound with both its physiologically relevant ligands, coenzyme A (CoA) and a histone H3 peptide, and the structures of nascent tGCN5 and a tGCN5/acetyl-CoA complex. Our structural data reveal histone-binding specificity for a random-coil structure containing a G-K-X-P recognition sequence, and show that CoA is essential for reorienting the enzyme for histone binding. Catalysis appears to involve water-mediated proton extraction from the substrate lysine by a glutamic acid general base and a backbone amide that stabilizes the transition-state reaction intermediate. Comparison with related N-acetyltransferases indicates a conserved structural framework for CoA binding and catalysis, and structural variability in regions associated with substrate-specific binding.
About this Structure
1QSN is a Protein complex structure of sequences from Saccharomyces cerevisiae and Tetrahymena thermophila with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of Tetrahymena GCN5 bound to coenzyme A and a histone H3 peptide., Rojas JR, Trievel RC, Zhou J, Mo Y, Li X, Berger SL, Allis CD, Marmorstein R, Nature. 1999 Sep 2;401(6748):93-8. PMID:10485713
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