物理化学学报
物理化學學報
물이화학학보
ACTA PHYSICO-CHIMICA SINICA
2011年
1期
207-212
,共6页
孙浩%蒋勇军%俞庆森%高慧
孫浩%蔣勇軍%俞慶森%高慧
손호%장용군%유경삼%고혜
GSK-3β激酶%磷酸化%Mg2+%结构金属离子%分子动力学模拟
GSK-3β激酶%燐痠化%Mg2+%結構金屬離子%分子動力學模擬
GSK-3β격매%린산화%Mg2+%결구금속리자%분자동역학모의
GSK-3β kinase%Phosphoryl transfer%Mg2+%Structural metal ion%Molecular dynamics simulation
糖原合成酶激酶-3β(GSK-3β)是一种丝氨酸/苏氨酸蛋白激酶,调节糖原合成酶的活性,并在生物体内的多条信号通路中发挥作用.GSK-3β是糖尿病,肿瘤,急性炎症,早老性痴呆等多种复杂疾病的药物作用靶标.Mg2+是GSK-3β激酶的保守结构金属离子,与三磷酸腺苷(ATP)分子作用,在激酶的磷酸化中扮演重要的角色,本文阐明了两个Mg2+离子(Mg2+Ⅰ,Mg2+Ⅱ)在激酶磷酸化中的作用:Mg2+稳定GSK-3β与ATP的构象.缺乏Mg2+离子,GSK-3β结构的柔性增强,同时ATP的构象发生改变,相对Mg2+Ⅱ离子而言,Mg2+Ⅰ离子在磷酸化反应中的作用更突出,但Mg2+Ⅱ离子也是必不可少的,如果没有Mg2+Ⅱ离子,Lys183无法独立稳定ATP的合适构象.当两个Mg2+离子都不存在时,ATP形成分子内的氢键,成为一种折叠的构象.
糖原閤成酶激酶-3β(GSK-3β)是一種絲氨痠/囌氨痠蛋白激酶,調節糖原閤成酶的活性,併在生物體內的多條信號通路中髮揮作用.GSK-3β是糖尿病,腫瘤,急性炎癥,早老性癡呆等多種複雜疾病的藥物作用靶標.Mg2+是GSK-3β激酶的保守結構金屬離子,與三燐痠腺苷(ATP)分子作用,在激酶的燐痠化中扮縯重要的角色,本文闡明瞭兩箇Mg2+離子(Mg2+Ⅰ,Mg2+Ⅱ)在激酶燐痠化中的作用:Mg2+穩定GSK-3β與ATP的構象.缺乏Mg2+離子,GSK-3β結構的柔性增彊,同時ATP的構象髮生改變,相對Mg2+Ⅱ離子而言,Mg2+Ⅰ離子在燐痠化反應中的作用更突齣,但Mg2+Ⅱ離子也是必不可少的,如果沒有Mg2+Ⅱ離子,Lys183無法獨立穩定ATP的閤適構象.噹兩箇Mg2+離子都不存在時,ATP形成分子內的氫鍵,成為一種摺疊的構象.
당원합성매격매-3β(GSK-3β)시일충사안산/소안산단백격매,조절당원합성매적활성,병재생물체내적다조신호통로중발휘작용.GSK-3β시당뇨병,종류,급성염증,조로성치태등다충복잡질병적약물작용파표.Mg2+시GSK-3β격매적보수결구금속리자,여삼린산선감(ATP)분자작용,재격매적린산화중분연중요적각색,본문천명료량개Mg2+리자(Mg2+Ⅰ,Mg2+Ⅱ)재격매린산화중적작용:Mg2+은정GSK-3β여ATP적구상.결핍Mg2+리자,GSK-3β결구적유성증강,동시ATP적구상발생개변,상대Mg2+Ⅱ리자이언,Mg2+Ⅰ리자재린산화반응중적작용경돌출,단Mg2+Ⅱ리자야시필불가소적,여과몰유Mg2+Ⅱ리자,Lys183무법독립은정ATP적합괄구상.당량개Mg2+리자도불존재시,ATP형성분자내적경건,성위일충절첩적구상.
Glycogen synthase kinase-3β (GSK-3β) is a kind of serine/threonine protein kinase. It regulates the synthesis of glycogen and plays an important part in several signal pathways. It is believed to be an important target for a number of diseases such as diabetes, cancers, chronic inflammation, and Alzheimer's disease. Mg2+ ions are conserved structural metal ions in GSK-3β and they interact with adenosine-triphosphate (ATP). They are very important in phosphoryl transfer in the kinase. In this paper,the effect of two Mg2+ ions (Mg2+|, Mg2+||) on GSK-3β is illustrated. Mg2+ can stabilize the conformation of GSK-3β and ATP. Without Mg2+, the stabilization of GSK-3β reduces explicitly and the conformation of ATP changes. Mg2+| is important in the phosphorylation reaction while Mg2+|| is essential and Lys183 alone cannot maintain the conformation of ATP without the assistance of Mg2+||. ATP forms intramolecular hydrogen bonds and adopts a folded conformation when both Mg2+| and Mg2+|| are absent.