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首页> 外文期刊>Journal of Molecular Biology >THE CRYSTAL STRUCTURE OF A HUMAN NUCLEOSIDE DIPHOSPHATE KINASE, NM23-H2
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THE CRYSTAL STRUCTURE OF A HUMAN NUCLEOSIDE DIPHOSPHATE KINASE, NM23-H2

机译：人核苷二磷酸激酶NM23-H2的晶体结构

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摘要

The 2.8 Angstrom resolution X-ray structure of NM23-H2 has been determined by molecular replacement using the structure of Myxococcus xanthus nucleoside diphosphate (NDP) kinase. NM23-H2 is a human NDP kinase. The enzyme catalyses phosphoryl transfer, binds DNA, and can activate the transcription of the c-myc oncogene in vitro. NM23 has also been reported to be a suppressor of metastasis in some types of tumours. Whereas the M. xanthus NDP kinase is a tetramer, NM23-H2 is a hexamer. The fold of NM23-H2 is identical to the fold of other NDP kinases. Two antiparallel helices joined by a turn form one edge of the nucleotide binding cleft. This region moves in a hinge-like fashion in response to substrate binding and crystal packing forces. Additional differences in conformation among the NDP kinases are principally in regions involved in protein-protein contacts within the oligomers. The only protein-protein interaction conserved among all NDP kinases is a dimeric interaction. Several mutations of NM23-H2 have been detected in tumour tissues. These mutations do not involve residues interacting with the substrates, and probably destabilise the enzyme without directly affecting the catalytic activity. Low level phosphorylation of serines has been reported for NM23 both in vitro and in vivo. The structure of the hexamer indicates that two serine residues that have been reported as being phosphorylated, Ser44 and Ser122, are on the surface of the hexamer, and are likely to be phosphorylated by exogenous kinases. In contrast, Ser120 is buried, and is most likely phosphorylated by a direct transfer from the phosphohistidine intermediate of the reaction mechanism. (C) 1995 Academic Press Limited [References: 41]
机译：NM23-H2的2.8埃分辨率X射线结构已通过使用粘胶球菌的双磷酸核苷二磷酸（NDP）激酶的分子置换来确定。 NM23-H2是人类NDP激酶。该酶催化磷酸基转移，结合DNA，并可以在体外激活c-myc癌基因的转录。据报道，NM23在某些类型的肿瘤中是转移的抑制剂。而黄单胞菌NDP激酶是四聚体，而NM23-H2是六聚体。 NM23-H2的倍数与其他NDP激酶的倍数相同。依次连接的两个反平行螺旋形成核苷酸结合裂隙的一个边缘。该区域响应于基板结合和晶体堆积力以铰链状移动。 NDP激酶之间构象的其他差异主要在寡聚体中涉及蛋白质-蛋白质接触的区域中。在所有NDP激酶中唯一保守的蛋白质-蛋白质相互作用是二聚体相互作用。在肿瘤组织中已经检测到NM23-H2的几个突变。这些突变不涉及与底物相互作用的残基，并且可能使酶不稳定，而不直接影响催化活性。在体外和体内均已报道了NM23的丝氨酸低水平磷酸化。六聚体的结构表明，已报道被磷酸化的两个丝氨酸残基Ser44和Ser122位于六聚体的表面，并很可能被外源激酶磷酸化。相反，Ser120被掩埋，最有可能被来自反应机理的磷酸组氨酸中间体的直接转移所磷酸化。 （C）1995 Academic Press Limited [参考号：41]

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