5HKI

Crystal structure of Mycobacterium tuberculosis H37Rv orotate phosphoribosyltransferase in complex with Fe(III) dicitrate

5HKI の概要

• エントリーDOI: 10.2210/pdb5hki/pdb
• 分子名称: Orotate phosphoribosyltransferase, Iron(III) dicitrate (3 entities in total)
• 機能のキーワード: oprt, de novo pyrimidine nucleotide synthesis, ferric dicitrate complex, transferase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 81679.41

構造登録者

Donini, S.,Ferraris, D.M.,Bolognesi, G.,Rizzi, M. (登録日: 2016-01-14, 公開日: 2017-01-25, 最終更新日: 2024-01-10)

主引用文献

Donini, S.,Ferraris, D.M.,Miggiano, R.,Massarotti, A.,Rizzi, M.
Structural investigations on orotate phosphoribosyltransferase from Mycobacterium tuberculosis, a key enzyme of the de novo pyrimidine biosynthesis.
Sci Rep, 7:1180-1180, 2017

PubMed Abstract: The Mycobacterium tuberculosis orotate phosphoribosyltransferase (MtOPRT) catalyses the conversion of α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and orotate (OA) in pyrophosphate and orotidine 5'-monophosphate (OMP), in presence of Mg. This enzyme is the only responsible for the synthesis of orotidine 5'-monophosphate, a key precursor in the de novo pyrimidine biosynthesis pathway, making MtOPRT an attractive drug target for the development of antitubercular agents. We report the crystal structures of MtOPRT in complex with PRPP (2.25 Å resolution), inorganic phosphate (1.90 Å resolution) and the exogenous compound Fe(III) dicitrate (2.40 Å resolution). The overall structure of the mycobacterial enzyme is highly similar to those described for other OPRTases, with the "flexible loop" assuming a well define conformation and making specific contacts with the Fe(III)-dicitrate complex. The structures here reported add to the knowledge of a potential drug target for tuberculosis, and will provide a useful tool for the structure-based drug design of potent enzyme inhibitors.

PubMed: 28446777
DOI: 10.1038/s41598-017-01057-z

実験手法

X-RAY DIFFRACTION (2.4 Å)