組蛋白乙酰化在調(diào)節(jié)細(xì)胞進(jìn)程中起著重要的作用,。釀酒酵母Rtt109是一類重要的組蛋白乙酰轉(zhuǎn)移酶（HATs）,，它能通過直接對(duì)新合成組蛋白H3賴氨酸56進(jìn)行乙酰化,，來促進(jìn)基因組穩(wěn)定（H3-K56）,，但其中的機(jī)制目前尚屬未知。
在10月8日的《結(jié)構(gòu)》（Structure）中,，Lin和Yuan等人報(bào)道了Rtt109的晶體結(jié)構(gòu)為2.2 Å,；而Rtt109/Acetyl-CoA復(fù)合體為1.9 Å的研究數(shù)據(jù),。Rtt109結(jié)構(gòu)為三層混合的α/ β模塊組成的中央模塊,，其核心區(qū)域的結(jié)構(gòu)與GCN5 HAT和P300/CBP HAT的結(jié)構(gòu)域相似,。通過結(jié)構(gòu)和生化分析，研究人員發(fā)現(xiàn)了Rtt109蛋白的催化活性部位,；確定了Asp288為去質(zhì)子殘基,；Lys290為自動(dòng)乙酰化殘基,。
Lin等人還在進(jìn)一步的研究中發(fā)現(xiàn)了獨(dú)特的蛋白H3-K56錨定袋和潛在的H3αN制動(dòng)槽,，從而揭開了Rtt109蛋白通過 H3-K56完成乙酰化的分子機(jī)制,。（生物谷Bioon.com）
生物谷推薦原始出處：
Structure,，Volume 16, Issue 10, 1503-1510, 8 October 2008，Chengqi Lin and Y. Adam Yuan
Structural Insights into Histone H3 Lysine 56 Acetylation by Rtt109
Chengqi Lin1andY. Adam Yuan1,,
1 Genome and Structural Biology Program, Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore
SUMMARY
Histone acetylation plays important roles for the regulation of many fundamental cellular processes. Saccharomyces cerevisiae Rtt109 is an important class of histone acetyltransferases (HATs), whichpromote genome stability by directly acetylating newly synthesized histone H3 lysine 56 (H3-K56) through an unknown mechanism. Here, we report the crystal structures of Rtt109 at 2.2 ? and Rtt109/Acetyl-CoA binary complex at 1.9 ?. The structure displaysa vise-like topology with mixed three-layered / module forming the central module, whose core region resembles the structure of GCN5 HAT domain and P300/CBP HAT domain. Using structural and biochemical analyses, we have discovered the catalytic active site and have identified Asp288 as the deprotonation residue and Lys290 as the autoacetylation residue. We have further proposed the unique H3-K56 anchoring pocket and the potential H3N binding groove. Our work has provided structural insights tounderstand the acetylation mechanism of H3-K56 by Rtt109.
