Elucidation of the Catalytic Function and the Inhibition mechanism of Phospholipase A_2
磷脂酶A_2的催化功能和抑制机制的阐明
基本信息
- 批准号:05671853
- 负责人:
- 金额:$ 1.28万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (C)
- 财政年份:1993
- 资助国家:日本
- 起止时间:1993 至 1994
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1. Effects of Ca^<2+> and pH on the kinetic parameter for the hydrolysis of monodispersed 1,2-dihexanoy1-sn-glycero-3-phosphorylcholine, catalyzed by Group I and II phospholipases A_2 (PLA_2s) , were studied by the pH-stat assay method in the absence or presence of carbonic amidetype, oxazolidinone-type, and sulfonic amide-type substrate analogs. The Ca^<2+> dependency and participation of the catalytic group His 48 in the binding of genuine substrate to both types of PLA_2s were found to be very similar to those of the oxazolidinone-type substrate analog, but differed greatly from the carbonic amide-type and sulfonic amide-type substrate analogs. This finding suggests that the binding mode of oxazolidinone-type substrate analog is very similar to that of the genuine substrate.2. Chemical modification and inactivation of Group I and II PLA_2s were investigated by the use of a manoalide (MLD) -analog. It was found that Lys-56 of bovine pancreatic PLA_2s was modified by MLD-analog and that this modification was responsible for enzyme inactivation. It was indicated that the inactivation of pancreatic and N.naja atra PLA_2s originated from the modification of Lys residues at the interfacial recognition site, and that the inactivation of P.australis, T.flavoviridis and V.russelli russelli PLA_2s arose from the modification of Lys residues at the catalytic site, interfacial recognition site and regions outside both sits. The inactivation of A.halys blomhoffii PLA_2s was assumed to be due to the modification of Lys residues outside the two sites described above. We thought that the modification of the Lys residues outside the above two sites give rise to conformational changes leading to inactivation
1. 研究了 Ca^2+ 和 pH 对 I 类和 II 类磷脂酶 A_2 (PLA_2s) 催化的单分散 1,2-二己酰基 1-sn-甘油-3-磷酸胆碱水解动力学参数的影响在不存在或存在碳酰胺型、恶唑烷酮型和磺酰胺型的情况下的pH-stat测定方法底物类似物。发现催化基团 His 48 在真正底物与两种类型 PLA_2 结合中的 Ca^2+ 依赖性和参与与恶唑烷酮型底物类似物非常相似,但与碳酰胺有很大不同-型和磺酰胺型底物类似物。这一发现表明恶唑烷酮型底物类似物的结合模式与真正的底物非常相似。 2.通过使用马诺内酯 (MLD) 类似物研究了 I 组和 II 组 PLA_2 的化学修饰和失活。发现牛胰腺PLA_2的Lys-56被MLD类似物修饰,并且这种修饰导致酶失活。表明胰腺和N.naja atra PLA_2s的失活源于界面识别位点Lys残基的修饰,而P.australis、T.flavoviridis和V.russelli russelli PLA_2s的失活源于界面识别位点Lys残基的修饰。催化位点、界面识别位点和两个位点外部区域的赖氨酸残基。 A.halys blomhoffii PLA_2s 的失活被认为是由于上述两个位点之外的 Lys 残基的修饰所致。我们认为上述两个位点之外的赖氨酸残基的修饰会引起构象变化,从而导致失活
项目成果
期刊论文数量(32)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
K.TOMOO: "X-Ray Crystal Structure and Molecular Dynamics Simulation of Bovine Pancreas Phospholipase A_2-n-Dodecylphosphorylcholine Complex." Proteins : Structure, Function and Genetics. 19. 330-339 (1994)
K.TOMOO:“牛胰腺磷脂酶 A_2-n-十二烷基磷酸胆碱复合物的 X 射线晶体结构和分子动力学模拟。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
K.TOMOO: "Crystallization and Preliminary X-Ray Study of Agkistrodon halys blomhoffii Phospholipase A_2 Complex with Specific Inhibitor" J.Biochem.113. 411-412 (1993)
K.TOMOO:“Agkistrodon halys blomhoffii 磷脂酶 A_2 复合物与特定抑制剂的结晶和初步 X 射线研究”J.Biochem.113。
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- 影响因子:0
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S.FUJII: "Chemical Modification and Inactivation of Phospholipase A_2 by a Manoalide Analogue." Biochem.J.(in press). (1995)
S.FUJII:“Manoalide 类似物对磷脂酶 A_2 进行化学修饰和灭活。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
T.TANI: "Binding Mode of Phospholipase A_2 with a New Type of Phospholiqid Analog Having an Oxazolidinone Ring." J.Biochem.117. 176-182 (1995)
T.TANI:“磷脂酶 A_2 与具有恶唑烷酮环的新型磷脂类似物的结合模式。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
S.FUJII: "Chemical Modification and Inactivation of Phospholipase A_2 by a Manoalide Analogue." Biochem.J.(in press).
S.FUJII:“Manoalide 类似物对磷脂酶 A_2 进行化学修饰和灭活。”
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- 发表时间:
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- 影响因子:0
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IKEDA Kiyoshi其他文献
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{{ truncateString('IKEDA Kiyoshi', 18)}}的其他基金
Synthesis and Biological Evaluations as Inhibitors of Human Parainfluenza Virus-1 based on the Computational Design for Prevention of Multi-infectious Diseases
基于预防多种传染病的计算设计的人类副流感病毒1抑制剂的合成和生物学评价
- 批准号:
24590155 - 财政年份:2012
- 资助金额:
$ 1.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Sialic acid derivative synthesis and inhibitory activities against human parainfluenza virus type 1
唾液酸衍生物的合成及其对人副流感病毒1型的抑制活性
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21590117 - 财政年份:2009
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$ 1.28万 - 项目类别:
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Synthesis of sialic acid derivatives for human parainfluenza virus type-1 sialidase inhibitors
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19590103 - 财政年份:2007
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Grant-in-Aid for Scientific Research (C)
Chemoenzymatic synthesis of N-acetylneuraminic acid derivatives and their behaviour towards sialidase from human parainfluenza virus
N-乙酰神经氨酸衍生物的化学酶合成及其对人副流感病毒唾液酸酶的行为
- 批准号:
13672223 - 财政年份:2001
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$ 1.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of simple apparatus for measuring liquid-concentration by ultrasonic light diffraction effect
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- 批准号:
12650051 - 财政年份:2000
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$ 1.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Elucidation of the Catalytic Function of Phospholipases
磷脂酶催化功能的阐明
- 批准号:
09672264 - 财政年份:1997
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$ 1.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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08672565 - 财政年份:1996
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$ 1.28万 - 项目类别:
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- 批准号:
07672399 - 财政年份:1995
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$ 1.28万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular Theory of the Catalytic Function of Phospholipase A2
磷脂酶A2催化功能的分子理论
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02671022 - 财政年份:1990
- 资助金额:
$ 1.28万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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