Crystal structure of the ternary complex of Leishmania major pteridine reductase 1 with the cofactor NADP⁺/NADPH and the substrate folic acid.

ABSTRACT: Pteridine reductase 1 (PTR1) is a key enzyme of the folate pathway in protozoan parasites of the genera Leishmania and Trypanosoma and is a valuable drug target for tropical diseases. This enzyme is able to catalyze the NADPH-dependent reduction of both conjugated (folate) and unconjugated (biopterin) pterins to their tetrahydro forms, starting from oxidized- or dihydro-state substrates. The currently available X-ray structures of Leishmania major PTR1 (LmPTR1) show the enzyme in its unbound, unconjugated substrate-bound (with biopterin derivatives) and inhibitor-bound forms. However, no structure has yet been determined of LmPTR1 bound to a conjugated substrate. Here, the high-resolution crystal structure of LmPTR1 in complex with folic acid is presented and the intermolecular forces that

SUBMITTER: Dello Iacono L 

PROVIDER: S-EPMC8996148 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature