An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes.

An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes.
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DOI:
10.1016/s0021-9258(18)47446-7
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发表时间:
1987-06
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
W. H. Busby;Gail E. Quackenbush;Jane Humm;W. Youngblood;John S. KizerS
W. H. Busby;Gail E. Quackenbush;Jane Humm;W. Youngblood;John S. KizerS
中科院分区:
其他
文献类型:
--
作者:
W. H. Busby;Gail E. Quackenbush;Jane Humm;W. Youngblood;John S. KizerS

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在新合成的多肽和蛋白质的N端,谷氨酰胺翻译后转化为焦谷氨酸的机制尚不清楚。报道了一种允许测量Gln-His-Pro-NH2到焦Glu-His-Pro-NH2(TRH)的转化率的方法。利用这一实验,我们证明了在生理条件下,这种多肽的N-末端谷氨酰胺的自发环化反应发生得很慢。此外,我们描述了一种酶(S)在大鼠脑、猪脑垂体和人B淋巴细胞中的存在,该酶能将Gln-His-Pro-NH2转化为焦Glu-His-Pro-NH2。该酶(S)似乎是一种糖蛋白,在中性pH下活性最高,Mr为55,000,并含有催化显著的巯基。酶反应产物用高分辨快原子轰击-质谱仪进行了确证。在初步研究中,我们发现牛肾上腺髓质中90%以上的酶存在于可溶的嗜铬囊泡部分中。这些发现表明,在体内,谷氨酰胺基肽翻译后转化为焦谷氨酰基肽既不是自发的,也不是先前提出的非生物的。
The mechanism for the post-translational conversion of glutamine to pyroglutamic acid on the N terminus of newly synthesized peptides and proteins is unknown. An assay is reported that permits measurement of the rate of conversion of Gln-His-Pro-NH2 to pyroGlu-His-Pro-NH2 (TRH). Using this assay, we demonstrate that the spontaneous cyclization of the N-terminal glutamine of this peptide occurs only slowly under physiological conditions. Furthermore, we describe the presence in rat brain, porcine pituitary, and human B lymphocytes of an enzyme(s) which converts Gln-His-Pro-NH2 into pyroGlu-His-Pro-NH2. The enzyme(s) appears to be a glycoprotein, is maximally active at neutral pH, has a Mr of 55,000, and contains catalytically significant sulfhydryl groups. The product of the enzymatic reaction was confirmed by high resolution fast atom bombardment-mass spectrometry. In preliminary studies, we find that over 90% of the enzyme in bovine adrenal medulla is contained in the soluble chromaffin vesicle fraction. These findings indicate that in vivo the post-translational conversion of a glutaminyl-peptide into a pyroglutamyl-peptide is neither spontaneous nor abiotic as has been previously proposed.