Functional Requirements for Inhibition of Thrombin by Antithrombin III in the Presence and Absence of Heparin*
Functional Requirements for Inhibition of Thrombin by Antithrombin III in the Presence and Absence of Heparin*
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在存在和不存在肝素的情况下抗凝血酶 III 抑制凝血酶的功能要求*
DOI：
10.1074/jbc.272.18.12024
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
C. Gibbs
中科院分区：
文献类型：
--
作者：
M. Tsiang;An Jain;C. Gibbs
79个高度暴露的氨基酸，包括约62%的溶剂可及表面的凝血酶鉴定的残基，调节凝血酶的抑制抗凝血酶III，凝血酶的主要生理抑制剂的突变。在存在和不存在肝素（W50 A，E229 A和R233 A）的情况下，降低凝血酶对抗凝血酶III抑制敏感性的突变也降低了小三肽基底物的水解。这些残基聚集在凝血酶的活性位点裂缝周围，并预测直接与抗凝血酶III的“底物环”相互作用。尽管抗凝血酶III（58 kDa）的大尺寸，没有残基以外的活性裂缝被确定直接与抗凝血酶III相互作用。在肝素存在但不存在的情况下，降低凝血酶对抗凝血酶III抑制敏感性的突变（R89 A/R93 A/E94 A、R98 A、R245 A、K248 A、K252 A/D255 A/Q256 A）一般也不影响三肽基底物的水解。这些残基聚集在凝血酶表面上的一片碱性残基之间，该表面垂直于含有活性位点裂缝的面，并预测直接与肝素相互作用。三个突变（E25 A、R178 A/R180 A/D183 A和E202 A）引起抗凝血酶III抑制作用的轻微增强。
Mutation of 79 highly exposed amino acids that comprise approximately 62% of the solvent accessible surface of thrombin identified residues that modulate the inhibition of thrombin by antithrombin III, the principal physiological inhibitor of thrombin. Mutations that decreased the susceptibility of thrombin to inhibition by antithrombin III in the presence and absence of heparin (W50A, E229A, and R233A) also decreased hydrolysis of a small tripeptidyl substrate. These residues were clustered around the active site cleft of thrombin and were predicted to interact directly with the “substrate loop” of antithrombin III. Despite the large size of antithrombin III (58 kDa), no residues outside of the active cleft were identified that interact directly with antithrombin III. Mutations that decreased the susceptibility of thrombin to inhibition by antithrombin III in the presence but not in the absence of heparin (R89A/R93A/E94A, R98A, R245A, K248A, K252A/D255A/Q256A) in general did not also affect hydrolysis of the tripeptidyl substrate. These residues were clustered among a patch of basic residues on a surface of thrombin perpendicular to the face containing the active site cleft and were predicted to interact directly with heparin. Three mutations (E25A, R178A/R180A/D183A, and E202A) caused a slight enhancement of inhibition by antithrombin III.
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影响因子：
56.9
作者：
BOWIE, JU;REIDHAAROLSON, JF;SAUER, RT
通讯作者：
SAUER, RT
凝血酶 B 插入环中的色氨酸 60-D 调节凝血酶-抗凝血酶反应。
DOI：
10.1021/bi952065y
发表时间：
1996
期刊：
Biochemistry.
影响因子：
--
作者：
Rezaie,AR
通讯作者：
Rezaie,AR
抗凝血酶：结构和功能。
影响因子：
3.6
作者：
Pratt,CW;Church,FC
通讯作者：
Church,FC
肝素辅因子 II 受变构调节，主要不是通过模板效应调节。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sheehan,JP;Tollefsen,DM;Sadler,JE
通讯作者：
Sadler,JE
DOI：
10.1073/pnas.88.16.7371
发表时间：
1991-08-01
影响因子：
11.1
作者：
LEBONNIEC, BF;ESMON, CT
通讯作者：
ESMON, CT