title: Theoretical study of specific hydrogen-bonding effects on the bridging P-OR bond strength of phosphate monoester dianions.
abstract: It has been proposed that the driving force for the initial phosphoryl transfer step of protein tyrosine phosphatases (PTPases) could be activation of the substrate ROPO32- by means of an enforced hydrogen-bonding interaction between an aspartic general acid and the bridging oxygen atom O (Zhang et al. Biochemistry 1995, 34, 16088-16096). The potential catalytic effect of this type of interaction, with regard to P-OR bond cleavage, was investigated computationally through simple model systems in which an efficient intramolecular hydrogen bond can take place between a H-bond donor group and the bridging oxygen atom of the dianionic phosphate. The dielectric effect of the environment (epsilon = 1, 4, and 78) was also explored. The results indicate that this interaction causes significant lengthenings of the scissile P-OR bond in all media but with more extreme effects observed in the low dielectric fields epsilon = 1 and epsilon = 4. It is interesting that, in all cases examined, this interaction actually contributes to stabilize the reactant state while causing its P-OR bond to lengthen. Overall, our results support the idea that this specific hydrogen-bonding situation might well be used by PTPases as an important driving force for promoting phosphoryl transfer reactions through highly dissociative transition states.
authors.affiliation: Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, UMR 5068 CNRS, Université Paul Sabatier, Toulouse Cedex 9, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Iché-Tarrat
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Barthelat
authors.forename: Alain
authors.initials: A
authors.lastname: Vigroux
mesh_terms: D000838:Anions / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry*; D012996:Solutions; D014867:Water / Q000737:chemistry
chemical_list: D000838:Anions; D003432:Cross-Linking Reagents; D004952:Esters; D010710:Phosphates; D012996:Solutions; D014867:Water