STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL

Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.

QEESILQDIITRFPNVVLMKQTAQLRAMMTIIRDKETPKEEFVFYADRLIRLLIEEALNELPFQKKEVTTPLDVSYHGVS
FYSKICGVSIVRAGESMESGLRAVCRGVRIGKILIQRDETTAEPKLIYEKLPADIRERWVMLLDPMCATAGSVCKAIEVL
LRLGVKEERIIFVNILAAPQGIERVFKEYPKVRMVTAAVDICLNSRYYIVPGIGDFGDRYFGTM

THE STRUCTURE HAS THREE SULPHATE MOLECULES (USED IN THE CRYSTALLIZATION). ONE SULPHATE IS BOUND IN THE ACTIVE SITE NEAR HELIX 5. THE SECOND SULPHATE ALSO BOUND NEAR THE ACTIVE SITE NEAR CIS-ARG RESIDUE (ARG112).

THERE IS A 5-FLUOROURACIL MOLECULE BOUND IN EACH SUBUNIT.

THERE IS A TETRAMER (CHAINS A,B,C,D) IN THE ASYMMETRIC UNIT. THE P21 SPACE GROUP CAN BE TRANSFORMED INTO C2221. WITH TWO IN THE ASU. THE STRUCTURE WAS SOLVED AS P21 FOR TECHNICAL REASONS.

TRANSFERASE, GLYCOSYLTRANSFERASE, PHOSPHORIBOSYLTRANSFERASE

MAQVPASGKLLVDPRYSTNDQEESILQDIITRFPNVVLMKQTAQLRAMMTIIRDKETPKEEFVFYADRLIRLLIEEALNE
LPFEKKEVTTPLDVSYHGVSFYSKICGVSIVRAGESMESGLRAVCRGCRIGKILIQRDETTAEPKLIYEKLPADIRDRWV
MLLDPMCATAGSVCKAIEVLLRLGVKEERIIFVNILAAPQGIERVFKEYPKVRMVTAAVDICLNSRYYIVPGIGDFGDRY
FGTM