Identification of Interaction Site of Propeptide toward Mature Carboxypeptidase Y (mCPY) Based on the Similarity between Propeptide and CPY Inhibitor (IC)

Identification of Interaction Site of Propeptide toward Mature Carboxypeptidase Y (mCPY) Based on the Similarity between Propeptide and CPY Inhibitor (IC)
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DOI:
10.1271/bbb.110668
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发表时间:
2012-01
期刊:
Bioscience, Biotechnology, and Biochemistry
影响因子:
--
通讯作者:
M. Nagayama;K. Kuroda;M. Ueda
M. Nagayama;K. Kuroda;M. Ueda
中科院分区:
其他
文献类型:
--
作者:
M. Nagayama;K. Kuroda;M. Ueda

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前体羧肽酶Y中的前肽(ProCPY)和成熟的cpy(MCPY)特异性内源性抑制物(IC)都能抑制cpy的活性。IC(IC的N-末端7个氨基酸)的N端抑制反应部位与mCPY的底物结合部位结合,是抑制mCPY所必需的,但其抑制mCPY的机制尚不清楚。在本研究中,IC和proCPY的序列比对表明,在proCPY中存在一个与IC的N-末端相似的序列。特别是,含有前肽C-末端的区域与IC的N-末端7个氨基酸相似。当IC的N端和前肽的C端相同的多肽存在时,cpy的活性受到竞争性抑制。前肽的C末端可能与mCPY的底物结合部位结合。
Both the propeptide in the precursor carboxypeptidase Y (proCPY) and the mature CPY (mCPY)-specific endogenous inhibitor (IC) inhibit CPY activity. The N-terminal inhibitory reactive site of IC (the N-terminal seven amino acids of IC) binds to the substrate-binding site of mCPY and is essential for mCPY inhibition, but the mechanism of mCPY inhibition by the propeptide is poorly understood. In this study, sequence alignment between IC and proCPY indicated that a sequence similar to the N-terminal region of IC was present in proCPY. In particular, a region including the C-terminus of the propeptide was similar to the N-terminal seven amino acids of IC. In the presence of peptides identical to the N-terminus of IC and the C-terminus of the propeptide, CPY activity was competitively inhibited. The C-terminal region of the propeptide might bind to the substrate-binding site of mCPY.