Enzyme Nomenclature News

June 2018

How to name atoms in phosphates, polyphosphates, their derivatives and mimics, and transition state analogues for enzyme-catalysed phosphoryl transfer reactions (IUPAC Recommendations 2016)

[Prepared by Gerry Moss]

The Protein Databank (PDB) includes many examples of phosphoryl transferase enzymes (EC 2.7) that contain phosphates or polyphosphates and their derivatives or mimics. A new IUPAC Recommendation published in Pure and Applied Chemistry* recommends how to identify and uniquely identify each atom of the phosphate or polyphosphate.

For monoesters the phosphorus atoms are identified as P^A, P^B, P^G, P^D, etc., starting from the ester end. For diesters the new recommendations explain how to determine which ester should be used to number the phosphorus atoms. When both a nucleic acid and a non-nucleic acid groups are present, the former takes precedence. If both are nucleic acid groups, then alphabetic order (A > C > G > T > U) is used.

With phosphate multi-esters, the phosphorus atoms are identified by the position at which they are attached. For example, in fructose 1,6-bisphosphate the two phosphorus atoms are named P¹ and P⁶. In polyphosphates the phosphorus atoms are named P^A1, P^B1, P^G1, etc.

The oxygen atom directly bonded to the sugar moiety is numbered using the number of the carbon it is attached to. For example, in ATP it is O^5′. The other three oxygen atoms of P^A are named O^1A, O^2A and O^3A, where O^3A bonds to P^B, O^1A is pro-R, and O^2A is pro-S.

When a terminal phosphoryl oxygen is replaced by sulfur, fluorine or nitrogen, the remaining two oxygen atoms are prochiral and are identified accordingly. For example, for ATP with a sulfur substitution, the sulfur atom is named S^1G and the two oxygens are O^2G (pro-R) and O^3G (pro-S).

Where the oxygen is hydrogen bonded to an adjacent amino acid (with bond length 3 Å), the primary sequence number of the amino acid is used to determine the oxygen numbering, as in O^1A, O^2A, O^3A, etc.

Other topics discussed in this recommendation include substitution by other atoms, trigonal bipyramidal phosphate transition state analogues, and metal coordination.

*Pure Applied Chem. 2017, 89(5), 653–675 DOI 10.1515/pac-2016-0202.

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