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首页> 外文期刊>Biochemistry >Effects of L-histidine and its structural analogues on human N-myristoyltransferase activity and importance of EEVEH amino acid sequence for enzyme activity
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Effects of L-histidine and its structural analogues on human N-myristoyltransferase activity and importance of EEVEH amino acid sequence for enzyme activity

机译：L-组氨酸及其结构类似物对人N-肉豆蔻酰基转移酶活性的影响以及EEVEH氨基酸序列对酶活性的重要性

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Myristoyl-COA:protein N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational transfer of myristate to the NH2-terminal glycine residue of a number of important proteins of diverse function. Human NMT (hNMT) activity was found to be activated by L-histidine in a concentration-dependent manner. In contrast, two structural analogues of L-histidine, L-histidinol and histamine, inhibited hNMT activity in a noncompetitive manner with half-maximal inhibitions of 18 and 1.5 mM, respectively. The inhibition of hNMT activity by L-histidinol was reversed by a 2-fold molar excess of L-histidine, suggesting that L-histidine and L-histidinol were competing for a common site on NMT. Kinetic data indicated that whereas L-histidine enhanced the V-max, bath L-histidinol and histamine decreased the V-max; none of these compounds altered the K-m. Our studies suggest that L-histidine and its analogues may be interacting with His-293, involved in myristoyl-CoA transfer, rather than His-218, and implicated in the transfer of myristoyl-CoA to the peptide substrates. Site-directed mutagenesis of His-293, Val-291, and Glu-290 resulted in proteins with no measurable NMT activity. The most conserved region in the catalytic domain EEVEH (289-293) is critical for the myristoyl-CoA transfer in the NMT-catalyzed reactions. This region will be useful for the design of regulators of NMT function. [References: 53]
机译：肉豆蔻酰基-COA：蛋白质N-肉豆蔻酰基转移酶（NMT）是一种必不可少的真核酶，催化肉豆蔻酸酯向许多功能多样的重要蛋白质的NH2末端甘氨酸残基的共翻译转移。发现人NMT（hNMT）活性被L-组氨酸以浓度依赖性方式激活。相比之下，L-组氨酸的两个结构类似物L-组氨酸和组胺以非竞争性方式抑制hNMT活性，最大抑制分别为18和1.5 mM。 L-组氨酸对hNMT活性的抑制作用被L-组氨酸的2倍摩尔过量逆转，表明L-组氨酸和L-组氨酸在NMT上竞争一个共同位点。动力学数据表明，虽然L-组氨酸提高了V-max，浴L-组氨酸和组胺却降低了V-max。这些化合物均未改变K-m。我们的研究表明，L-组氨酸及其类似物可能与His-293相互作用，参与了肉豆蔻酰辅酶A的转移，而不是His-218，并参与了肉豆蔻酰辅酶A到肽底物的转移。 His-293，Val-291和Glu-290的定点诱变导致蛋白质没有可测量的NMT活性。催化域EEVEH（289-293）中最保守的区域对于NMT催化反应中肉豆蔻酰辅酶A的转移至关重要。该区域对于NMT功能调节器的设计很有用。 [参考：53]

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