Is the Vanadate Anion an Analogue of the Transition State of RNAse A?

M. Krauss, Harold Basch

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30 Scopus citations

Abstract

The electronic structures of models of the monoanion phosphorane transition state in ribonuclease A and its putative vanadate transition-state analogue are compared. The electrostatic potential and gross atomic populations agree well for the vanadium and phosphorus trigonal-bipyramidal transition-state structures for both equatorial and axial bonds to hydroxyl ligands but are different for the V-O and P-O bonds. The P-O bond is semiionic but V-O is a multiple bond that is much less polar. A similar difference in the polarity between P-O and V-O is found for the dianion. Ionic hydrogen bonds to the cationic residues will not be comparable between the V-O and P-O bonds. The vanadium compound is not a transition-state analogue for such H-bonds. The pattern of Lys-41 and His-12 residue bonding observed for the vanadate-inhibited RNase A should not be used to analyze the mechanism. Proton transfer between the five-coordinate transition state and the His-119 residue is a step in both the cyclization and hydrolysis phases of the mechanism. The proton transfer curve from the equatorial hydroxyl ligand to a model of His-119 is calculated to be essentially equivalent for the vanadium and phosphorus five-coordinate models of the active site. Residue binding to the vanadate monoanion would be analogous to stabilization of the transition-state intermediate. Stable vanadium dianion intermediates, which are electronic analogues of the dissociative phosphorus dianion, are calculated with both equatorial-equatorial and equatorial-axial deprotonated oxygen sites. The equatorial-axial dianion is lowest in energy and accounts for the binding of the His-119 residue in the vanadium system although the binding is weaker than for the phosphorus analogue.

Original languageEnglish
Pages (from-to)3630-3634
Number of pages5
JournalJournal of the American Chemical Society
Volume114
Issue number10
DOIs
StatePublished - 1 May 1992

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