Minimal antizyme peptide fully functioning in the binding and inhibition of ornithine decarboxylase and antizyme inhibitor.
Minimal antizyme peptide fully functioning in the binding and inhibition of ornithine decarboxylase and antizyme inhibitor.
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DOI：
10.1371/journal.pone.0024366
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hung HC
中科院分区：
文献类型：
--
作者：
Hsieh JY;Yang JY;Lin CL;Liu GY;Hung HC
抗酶（AZ）是一种由228个氨基酸残基组成的蛋白质，通过与鸟氨酸脱羧酶（ODC）结合并解离其同源二聚体来调节ODC，从而抑制其酶活性。抗酶抑制剂（AZI）与ODC同源，但与AZ的亲和力高于ODC。在这项研究中，我们定量AZ和ODC以及AZ和AZI之间的生物分子相互作用，以确定功能AZ肽，可以结合ODC和AZI，并有效地抑制其功能的全长AZ蛋白。对于这些AZ肽，AZ_95-228的抑制能力与AZ_WT相似。此外，AZ_95-176显示出与AZ-95-228（IC 50：0.16 µM）相似的抑制作用（IC 50：0.20 µM），尽管缺失了跨越残基177-228的大片段。然而，从N-末端或C-末端进一步缺失AZ_95-176降低了其抑制ODC的能力。AZ_100-176和AZ_95-169肽抑制ODC的能力显著降低，IC 50值分别为0.43和0.37 µM。AZ_95-228、AZ_100-228和AZ_95-176肽的IC 50值与AZ_WT相当，并形成Kd、AZ-ODC值分别为1.5、5.3和5.6 µM的AZ-ODC复合物。重要的是，我们的数据还表明，AZI可以拯救AZ肽抑制的ODC酶活性，并且它可以以比ODC更高的亲和力结合AZ肽。总之，这些数据表明，这些截短AZ蛋白保留其AZI结合能力。因此，我们认为AZ_95-176是在ODC和AZI结合和抑制其功能中完全起作用的最小AZ肽。
Antizyme (AZ) is a protein with 228 amino acid residues that regulates ornithine decarboxylase (ODC) by binding to ODC and dissociating its homodimer, thus inhibiting its enzyme activity. Antizyme inhibitor (AZI) is homologous to ODC, but has a higher affinity than ODC for AZ. In this study, we quantified the biomolecular interactions between AZ and ODC as well as AZ and AZI to identify functional AZ peptides that could bind to ODC and AZI and inhibit their function as efficiently as the full-length AZ protein. For these AZ peptides, the inhibitory ability of AZ_95-228 was similar to that of AZ_WT. Furthermore, AZ_95-176 displayed an inhibition (IC50: 0.20 µM) similar to that of AZ-95-228 (IC50: 0.16 µM), even though a large segment spanning residues 177–228 was deleted. However, further deletion of AZ_95-176 from either the N-terminus or the C-terminus decreased its ability to inhibit ODC. The AZ_100-176 and AZ_95-169 peptides displayed a noteworthy decrease in ability to inhibit ODC, with IC50 values of 0.43 and 0.37 µM, respectively. The AZ_95-228, AZ_100-228 and AZ_95-176 peptides had IC50 values comparable to that of AZ_WT and formed AZ-ODC complexes with K d,AZ-ODC values of 1.5, 5.3 and 5.6 µM, respectively. Importantly, our data also indicate that AZI can rescue AZ peptide-inhibited ODC enzyme activity and that it can bind to AZ peptides with a higher affinity than ODC. Together, these data suggest that these truncated AZ proteins retain their AZI-binding ability. Thus, we suggest that AZ_95-176 is the minimal AZ peptide that is fully functioning in the binding of ODC and AZI and inhibition of their function.
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影响因子：
8
作者：
Iwata, S;Sato, Y;Mizutani, S
通讯作者：
Mizutani, S
影响因子：
64.8
作者：
AUVINEN, M;PAASINEN, A;HOLTTA, E
通讯作者：
HOLTTA, E
DOI：
10.1073/pnas.070055897
发表时间：
2000-04-25
影响因子：
11.1
作者：
Ivanov, IP;Rohrwasser, A;Atkins, JF
通讯作者：
Atkins, JF
影响因子：
14.9
作者：
Ivanov, IP;Gesteland, RF;Atkins, JF
通讯作者：
Atkins, JF
影响因子：
56.9
作者：
GHODA, L;WETTERS, TV;COFFINO, P
通讯作者：
COFFINO, P