Inert cobalt complexes as mechanistic probes of the biochemistry of magnesium cofactors. Application to topoisomerase I

Metal Activation of Enzymes in Nucleic Acid Biochemistry

“…Catalytic activation of E. coli ribonuclease H by a series of inert chromium complexes [Cr(NH 3 ) 6-x (H 2 O) x ] 3+ (x ) 0-6) that bear water and ammonia ligands in well-defined geometries in the inner coordination shell has been examined. 16,35 This approach has been applied also to E. coli exonuclease III, 35 topoisomerase I, 70 and other enzymes and ribozymes 9,71 to establish outer-sphere pathways. Such complexes are observed to function by transition-state stabilization, and the approach permits one to distinguish hydrogen bonding from electrostatic contributions inasmuch as NH 3 bound to Cr(III) or Co(III) centers has negligible H-bonding propensity.…”

Probing RNA hairpins with cobalt(III)hexammine and electrospray ionization mass spectrometry

“…Cowan [10] proposed that Co(NH 3 ) 6 3ϩ could serve as a probe of Mg(H 2 O) 6 2ϩ binding sites, because both ions have similar ionic radii and geometries, and interact with RNA in a similar manner ( Figure 1) [4,5,[11][12]. More specifically, Co(NH 3 ) 6 3ϩ can substitute for the Mg(H 2 O) 6 2ϩ outer coordination sphere contacts with RNA [4,10,13]. NMR spectroscopy has typically been the method of choice to study Co(NH 3 ) 6 3ϩ interactions with RNA, but it is timeconsuming and requires large quantities of sample.…”

Transition Metals as Probes of Metal Cofactors in Nucleic Acid Biochemistry

“…To address this issue, we and others have employed inert complexes of defined coordination state to investigate the functional role of magnesium ion. [40][41][42][43][44][45][46] In the remainder of the article we highlight some strategies (old and new) that provide some chemical insights into the biochemistry of this ion.…”