Zn-, Cd-, and Pb-transcription factor IIIA: properties, DNA binding, and comparison with TFIIIA-finger 3 metal complexes

Huang, ML, Krepkiy, D, Hu, WN, Petering, DH
JOURNAL OF INORGANIC BIOCHEMISTRY 98,  775 - 785 (2004)
Times cited: 38

Abstract

Properties of the metal ion binding sites of Zn-transcription factor IIIA (TFIIIA) were investigated to understand the potential of this type of zinc finger to undergo reactions that remove Zn2+ from the protein. Zn-TFIIIA was purified from E coli containing the cloned sequence for Xenopus laevis oocyte TFIIIA and its stoichiometry of bound Zn2+ was shown to depend on the details of the isolation process. The average dissociation constant of Zn2+ in Zn-TFIIIIA was 10(–7). The dissociation constant for Zn-F3, the third finger from the N-terminus of TFIIIA, was 1.0 x 10(–8). The reactivity of Zn-TFIIIA with a series of metal binding ligands, including 2-carboxy-2’-hydroxy-5’sulfoformazylbenzene (zincon), 4(2-pyridylazo)resorcinol (PAR), and 3-ethoxy-2-oxo-butyraldehyde-bis(N-4-dimethylthiosemicarbazone) (H2KTSM2) revealed similar kinetics. The reactivity of PAR with Zn-TFIIIA declined substantially when the protein was bound to the internal control region (ICR) of the 5S ribosomal DNA. Both Cd2+ and Ph2+ disrupt TFIIIA binding to its cognate DNA sequence. The Ph2+ dissociation constant of Pb-F3 was measured as 2.5 x 10(–8). According to NMR spectroscopy, F3 does not fold into a regular conformation in the presence of Pb2+.