Journal:Acta Cryst F:S2053230X18018083

An assessment of three human methylenetetrahydrofolate dehydrogenase/cyclohydrolase ligand complexes following further refinement

Renata V. Bueno, Alice Dawson and William N. Hunter ^[1]

Molecular Tour
Further refinement of three methylenetetrahydrofolate dehydrogenase/cyclohydrolase antifolate inhibitor complexes in the Protein Data Bank has produced models that allow for a critical reassessment of ligand placement.

One complex has a well-ordered ligand in a catalytic site and the model provides an improved description of enzyme-inhibitor interactions (1dib: ). One ligand may adopt two conformations in the binding site rather than the single one previously described (1dia: ; 1st conformation is colored in wheat and 2nd conformation is in magenta). There is no evidence to support incorporation of the third compound in the model (1dig:L37). Our interpretation of the data supports a correlation between the models and inhibition activity for two of the compounds. In the case of the third, inconsistencies are noted that would need to be addressed by further work.

References

1. ↑ Bueno R, Dawson A, Hunter WN. An assessment of three human methylenetetrahydrofolate dehydrogenase/cyclohydrolase-ligand complexes following further refinement. Acta Crystallogr F Struct Biol Commun. 2019 Mar 1;75(Pt 3):148-152. doi:, 10.1107/S2053230X18018083. Epub 2019 Feb 20. PMID:30839287 doi:http://dx.doi.org/10.1107/S2053230X18018083