Project Details Nomenclature of Transition State Structures and their Analogs for Phosphoryl Transfer Reactions

Project No.:
2013-039-2-300
Start Date:
01 October 2013
End Date:
31 May 2017
Division Name:
Organic and Biomolecular Chemistry Division
Division No.:
300

Objective

This project seeks to establish a rational, logical, and practical system of nomenclature to identify discrete axial and equatorial ligands in both trigonal bipyramidal (tbp) and octahedral transition states (TSs) and their analogues for phosphoryl transfer reactions. In many cases, these will be chirally defined only as a result of coordination to components of the enzyme active site where they are located. It will apply to TSs for “in-line” and/or for (theoretical) “adjacent” attack systems and be independent of considerations about “associative” and “dissociative” TSs. It will link to established IUPAC nomenclature systems and usage, in particular to IUPAC Red Book (2005). It will aim to be directly comprehensible to and useable by Stakeholders.

Description

Structural studies of transition states for phosphoryl transfer reactions originated in protein crystallography in the late 1990s (Xu, Y.W., et al., (1997) PNAS, 94, 3579-83). They have focused on stable inorganic mimics for the pentaco-ordinate TS resulting in >70 entries in the Protein Data Bank (PDB) for vanadate complexes (ligand VO4), >80 entries for tetrafluoroaluminate (ALF), and 15 entries for trifluoromagnesate (MGF). Additionally, there are 63 tbp transition state analogues complexes assigned as trifluoroaluminum (AF3) though some of these have been shown to be MGF complexes. A third dimension comes from the expanding body of work based on computational analysis (QM-MM, DFT, EVB, etc.) and of enzyme-catalysed phosphoryl transfer systems, which tend to use the identification system employed in the experimental publication from which their work derives.

As yet, there is no systematic nomenclature system for identification of ligands around the central phosphorus/metal core of the tbp or octahedral (for ALF) complex.

Nomenclature systems hitherto adopted by protein crystallographers have no common rational basis. The system currently adopted in 19F NMR studies is ad hoc, (the most downfield resonance is assigned “A” and progresses upfield to “C” (tbp) or “D” (octahedral). In complexes for inositol polyphosphate systems, the number of fluoride ligands can rise higher. This utilitarian NMR system does not map rationally on any of the crystallographic systems of nomenclature.

Progress

December 2015 update – The Group of experts formulated a general plan for the Project which was discussed at a 2-day workshop in Malaga in November 2014. All aspects of the Project were analysed and proposals formulated for its specific development, with contributions from individual members according to their expertise. Sub-group meetings in London, Paris, and Sheffield were held to polish various sections of the Report, which was finalised for submission to IUPAC in December 2015.

February 2016 update – A manuscript titled ‘How to Name Atoms in Phosphates, Polyphosphates, their Analogues, and Transition State Analogues for Enzyme-catalysed Phosphoryl Transfer Reactions’ was made available as provisional recommendations and for public review until 30 June 2016.

Jan 2017 update – The revisions requested by the reviewers were exhaustively analysed, particularly to resolve interdisciplinary problems between IUPAC and IUBMB on conflicting aspects of nomenclature established by usage in their contrasting communities. The review process identified some problems at the interface between chemistry and molecular biology that need resolution. In the event, and after valuable conciliatory work by the Editor of PAC, Dr. Ron Weir, an agreed final text was accepted in December 2016. The final manuscript was submitted to production in January 2017 and will appear in Pure and Applied Chemistry.

May 2017 update – “How to name atoms in phosphates, polyphosphates, their derivatives and mimics, and transition state analogues for enzyme-catalysed phosphoryl transfer reactions (IUPAC Recommendations 2016)” is published as Pure and Applied Chemistry, 89(5), pp. 653-675, 2017. https://doi.org/10.1515/pac-2016-0202

Project completed

Page last updated: 5 June 2017