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Nature communication：利用配体诱导的活性位点重排抑制Sirt2

2015-02-17 佚名 生物谷

SIRT2活性位点
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近日，著名国际期刊Nature Communication发表了德国科学家的一项最新研究成果，他们通过结构生物学方法，分析了Sirt2及其特异性抑制剂形成的复合物的结构，发现sirt2特异性抑制剂能够诱导Sirt2活性位点重排影响其酶活性。 研究人员指出，Sirtuins是一类高度保守的NAD+依赖性赖氨酸去乙酰化酶。之前研究发现Sirt2在人类癌症，炎症和神经退化方面都有重要作用，因此，调

近日，著名国际期刊Nature Communication发表了德国科学家的一项最新研究成果，他们通过结构生物学方法，分析了Sirt2及其特异性抑制剂形成的复合物的结构，发现sirt2特异性抑制剂能够诱导Sirt2活性位点重排影响其酶活性。

研究人员指出，Sirtuins是一类高度保守的NAD+依赖性赖氨酸去乙酰化酶。之前研究发现Sirt2在人类癌症，炎症和神经退化方面都有重要作用，因此，调节Srit2活性成为实行药物干预的一项非常具有前景的治疗策略，但目前对于Sirt2抑制因子的研究还相对缺乏。
 
研究人员通过对人类Sirt2及其高度特异性的抑制剂形成的复合物进行高分辨率结构解析找到了抑制剂专一性抑制Sirt2活性的具体机制。他们发现抑制剂对Sirt2的选择性和强力作用是基于配体诱导的对sirt2结构中一个新发现的结合口袋进行结构重排而实现的。应用一种叫做SriReal2的强力sirtuin-重排配体，可以导致Hela细胞中微管高度乙酰化，同时诱导检验点蛋白BubR1的不稳定，这与体内抑制Sirt2表型一致。
 
研究人员通过结构生物学方法深入探究了选择性抑制Sirtuin的具体机制，这为进一步开发sirtuin抑制剂提供了重要基础。

原始出处

Rumpf T1, Schiedel M1, Karaman B2, Roessler C3, North BJ4, Lehotzky A5, Oláh J5, Ladwein KI1, Schmidtkunz K1, Gajer M1, Pannek M6, Steegborn C6, Sinclair DA4, Gerhardt S7, Ovádi J5, Schutkowski M3, Sippl W2, Einsle O7, Jung M1.elective Sirt2 inhibition by ligand-induced rearrangement of the active site.Nat Commun. 2015 Feb

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    2015-02-20 yuhaisheng_ibp_32061711

    #SIRT2#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1984849, encodeId=2023198484911, content=<a href='/topic/show?id=62191634516' target=_blank style='color:#2F92EE;'>#SIRT2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16345, encryptionId=62191634516, topicName=SIRT2)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bb182500058, createdName=yuhaisheng_ibp_32061711, createdTime=Fri Feb 20 10:11:00 CST 2015, time=2015-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880512, encodeId=3dcd1880512ca, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Aug 18 12:11:00 CST 2015, time=2015-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086767, encodeId=379f2086e6743, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Mon Nov 23 13:11:00 CST 2015, time=2015-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16573, encodeId=9a21165e332, content=很不错学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f2fb1607679, createdName=orthoW, createdTime=Fri Feb 20 09:14:00 CST 2015, time=2015-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16574, encodeId=f4fa165e401, content=很不错学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f2fb1607679, createdName=orthoW, createdTime=Fri Feb 20 09:14:00 CST 2015, time=2015-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16560, encodeId=82491656057, content=?学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f2fb1607679, createdName=orthoW, createdTime=Thu Feb 19 23:30:00 CST 2015, time=2015-02-19, status=1, ipAttribution=)]
    2015-08-18 liye789132251

    #Nat#

    0

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    2015-11-23 liuli5079

    #COMMUN#

    0

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    2015-02-20 orthoW

    很不错学习了

    0

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    2015-02-20 orthoW

    很不错学习了

    0

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    2015-02-19 orthoW

    ?学习了

    0

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