This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 14: | Line 14: | ||
[[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]] | ||
| Line 28: | Line 28: | ||
[[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
|
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
Page seeded by OCA on Thu Feb 21 14:43:14 2008
