Giraud Marie-France, Georgescauld Florian, Lascu Ioan, Dautant Alain
Institut de Biochimie et Génétique Cellulaires, UMR 5095 CNRS-Université Victor Segalen Bordeaux 2, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.
J Bioenerg Biomembr. 2006 Aug;38(3-4):261-4. doi: 10.1007/s10863-006-9043-0. Epub 2006 Sep 1.
Nm23 was the first metastasis suppressor gene identified. This gene encodes a NDP kinase that also exhibits other properties like histidine protein kinase and interactions with proteins and DNA. The S120G mutant of NDPK-A has been identified in aggressive neuroblastomas and has been found to reduce the metastasis suppressor effect of Nm23. In order to understand the differences between the wild type and the S120G mutant, we have determined the structure of both mutant and wild type NDPK-A in complex with ADP. Our results reveal that there are no significant changes between the two enzyme versions even in the surroundings of the catalytic histidine that is required for NDP kinase activity. This suggests that the S120G mutation may affect an other protein property than NDP kinase activity.
Nm23是首个被鉴定出的转移抑制基因。该基因编码一种NDP激酶，它还具有其他特性，如组氨酸蛋白激酶以及与蛋白质和DNA的相互作用。已在侵袭性神经母细胞瘤中鉴定出NDPK - A的S120G突变体，并且发现它会降低Nm23的转移抑制作用。为了了解野生型和S120G突变体之间的差异，我们确定了与ADP结合的突变型和野生型NDPK - A的结构。我们的结果表明，即使在NDP激酶活性所需的催化组氨酸周围环境中，这两种酶变体之间也没有显著变化。这表明S120G突变可能影响的是除NDP激酶活性之外的其他蛋白质特性。
