Crystal structures of S120G mutant and wild type of human nucleoside diphosphate kinase A in complex with ADP.
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.
Giraud
Marie-France
MF
Institut de Biochimie et Génétique Cellulaires, UMR 5095 CNRS-Université Victor Segalen Bordeaux 2, 1 rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.
Georgescauld
Florian
F
Lascu
Ioan
I
Dautant
Alain
A
D000244:Adenosine Diphosphate / Q000737:chemistry*; D003460:Crystallization; D006801:Humans; D008958:Models, Molecular; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry*; D014961:X-Ray Diffraction
D054778:NM23 Nucleoside Diphosphate Kinases; D000244:Adenosine Diphosphate; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase