A preliminary X-ray study of human nucleoside diphosphate kinase A under oxidative conditions.
Nucleoside diphosphate kinase (NDPK) catalyzes transfer of the γ-phosphoryl group from a nucleoside triphosphate (NTP) to a nucleoside diphosphate. The high-energy phosphate for this reaction is usually supplied by ATP. NDPK plays a primary role not only in maintaining cellular pools of all NTPs but also in the regulation of important cellular processes. NDPK-A (or Nm23-H1), one of eight human NDPKs, acts as a metastasis suppressor for some tumour types. A recent study showed that homohexameric human NDPK-A is regulated in response to oxidative stress. The activity of NDPK-A is reduced, with a concomitant increase in the population of dimeric NDPK-A, under oxidative conditions. In this study, human NDPK-A has been crystallized under oxidative conditions and X-ray data have been collected to 2.80 Å resolution using synchrotron radiation. The crystal belonged to the primitive cubic space group P2(1)3, with unit-cell parameters a = b = c = 106.8 Å. There is one NDPK-A dimer in the asymmetric unit. The preliminary electron-density map shows a large conformational change of the C-terminal domain of NDPK-A induced by a novel disulfide bond that is formed under oxidative conditions.
College of Pharmacy, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
Mi Sun
MS
Kim
Jihye
J
Jeong
Kong Joo
KJ
Lee
Dong Hae
DH
Shin
D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D054778:NM23 Nucleoside Diphosphate Kinases / Q000737:chemistry*; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary
D054778:NM23 Nucleoside Diphosphate Kinases