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多底物类似物对脑己糖激酶的抑制作用源于其与一个离散调控位点的结合。

Inhibition of brain hexokinase by a multisubstrate analog results from binding to a discrete regulatory site.

作者信息

Manning T A, Wilson J E

出版信息

Biochem Biophys Res Commun. 1984 Jan 13;118(1):90-6. doi: 10.1016/0006-291x(84)91071-4.

DOI:10.1016/0006-291x(84)91071-4
PMID:6696770
Abstract

P1-(adenosine-5')-P3-(glucose-6)-triphosphate (Ap3glucose) is a linear uncompetitive inhibitor vs glucose and a linear mixed inhibitor vs ATP of brain hexokinase, an inhibition pattern inconsistent with binding of Ap3glucose to the catalytic site when either the rapid equilibrium random or ordered sequential mechanism, which have been proposed for this enzyme, is considered. It is concluded that inhibition results from binding to a discrete regulatory site. The apparent ability of the regulatory site to accommodate both hexose and nucleotide moieties is consistent with suggestions by previous investigators that the regulatory site on mammalian hexokinases may have evolved from what was originally a catalytic site.

摘要

P1-(腺苷-5')-P3-(葡萄糖-6)-三磷酸(Ap3葡萄糖)对脑己糖激酶而言,对葡萄糖是线性非竞争性抑制剂,对ATP是线性混合型抑制剂,当考虑该酶已被提出的快速平衡随机或有序顺序机制时,这种抑制模式与Ap3葡萄糖结合到催化位点不一致。得出的结论是,抑制作用是由于与一个离散的调节位点结合所致。调节位点容纳己糖和核苷酸部分的明显能力与先前研究者的建议一致,即哺乳动物己糖激酶上的调节位点可能是从最初的催化位点进化而来的。

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1
Inhibition of brain hexokinase by a multisubstrate analog results from binding to a discrete regulatory site.多底物类似物对脑己糖激酶的抑制作用源于其与一个离散调控位点的结合。
Biochem Biophys Res Commun. 1984 Jan 13;118(1):90-6. doi: 10.1016/0006-291x(84)91071-4.
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Inhibition of hexokinase by multisubstrate analogs.
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Isolation and characterization of the discrete N- and C-terminal halves of rat brain hexokinase: retention of full catalytic activity in the isolated C-terminal half.大鼠脑己糖激酶离散的N端和C端片段的分离与特性分析:分离得到的C端片段保留完全催化活性
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Studies on the mechanism of orthophosphate regulation of bovine brain hexokinase.正磷酸盐对牛脑己糖激酶调节机制的研究。
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Allosteric inhibition of brain hexokinase by glucose 6-phosphate in the reverse reaction.在逆反应中,6-磷酸葡萄糖对脑己糖激酶的变构抑制作用。
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Binding of nucleoside triphosphates, inorganic phosphate, and other polyanionic ligands to the N-terminal region of rat brain hexokinase: relationship to regulation of hexokinase activity by antagonistic interactions between glucose 6-phosphate and inorganic phosphate.
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Rat brain hexokinase: further studies on the specificity of the hexose and hexose 6-phosphate binding sites.大鼠脑己糖激酶:对己糖及6-磷酸己糖结合位点特异性的进一步研究
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Inactivation of brain hexokinase by an adenosine 5'-triphosphate analog.一种腺苷5'-三磷酸类似物对脑己糖激酶的失活作用。
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Acidic phospholipids may inhibit rat brain hexokinase by interaction at the nucleotide binding site.酸性磷脂可能通过在核苷酸结合位点相互作用来抑制大鼠脑己糖激酶。
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Protein Sci. 2014 Jul;23(7):915-22. doi: 10.1002/pro.2473. Epub 2014 Apr 30.