Solution structure of the catalytic domain of GCN5 histone acetyltransferase bound to coenzyme A

被引:81
作者
Lin, YX
Fletcher, CM
Zhou, JX
Allis, CD
Wagner, G
机构
[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[2] MIT, Harvard Ctr Magnet Resonance, Cambridge, MA 02139 USA
[3] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA
[4] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA
关键词
D O I
10.1038/21922
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Gene transcription requires the release of inactive DNA from its packaging of histone proteins. Following the discovery of the first transcription-associated histone acetyltransferase, tetrahymena GCN5(1), it was shown that yeast GCN5 is recruited to the promoter and causes hyper-acetylation of histones and transcriptional activation of target genes(2,3), establishing a direct connection between histone acetylation and transcriptional activation. Many other important transcription regulators have been found to have histone acetyltransferase activity, including TAFII230/250, p300/CBP and its associated factor PCAF(4-9). Here we present the solution structure of the catalytic domain of tGCN5 (residues 47-210) in complex with coenzyme A. The structure contains two domains; the amino-terminal domain is similar to those of other GCN5-related N-acetyltransferases(10,11) but the carboxy-terminal domain is not. Coenzyme A binds in a deep hydrophobic pocket between the two domains. Chemical shift changes upon titration with histone H3 peptides indicate a binding site at the domain boundary opposite to the coenzyme A site. The structural data indicate a single-step acetyl-transfer reaction mechanism catalysed by a hydrogen bond to the backbone amide group of leucine 126 and the side-chain carboxyl group of a conserved acidic residue.
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页码:86 / 89
页数:4
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