5HKF

Crystal structure of Mycobacterium tuberculosis H37Rv orotate phosphoribosyltransferase in complex with 5-phospho-alpha-D-ribosyl 1-diphosphate (PRPP)

Summary for 5HKF

• Entry DOI: 10.2210/pdb5hkf/pdb
• Descriptor: Orotate phosphoribosyltransferase, 1-O-pyrophosphono-5-O-phosphono-alpha-D-ribofuranose (3 entities in total)
• Functional Keywords: transferase, oprt, de novo pyrimidine nucleotide synthesis, prpp complex
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 41185.80

Authors

Donini, S.,Ferraris, D.M.,Bolognesi, G.,Rizzi, M. (deposition date: 2016-01-14, release date: 2017-01-25, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.25 Å)