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5hkl

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Crystal structure of Mycobacterium tuberculosis H37Rv orotate phosphoribosyltransferase in complex with inorganic phosphate

Structural highlights

5hkl is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.899Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PYRE_MYCTU Catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate to orotate, leading to the formation of orotidine monophosphate (OMP).

Publication Abstract from PubMed

The Mycobacterium tuberculosis orotate phosphoribosyltransferase (MtOPRT) catalyses the conversion of alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and orotate (OA) in pyrophosphate and orotidine 5'-monophosphate (OMP), in presence of Mg(2+). 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 A resolution), inorganic phosphate (1.90 A resolution) and the exogenous compound Fe(III) dicitrate (2.40 A 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.

Structural investigations on orotate phosphoribosyltransferase from Mycobacterium tuberculosis, a key enzyme of the de novo pyrimidine biosynthesis.,Donini S, Ferraris DM, Miggiano R, Massarotti A, Rizzi M Sci Rep. 2017 Apr 26;7(1):1180. doi: 10.1038/s41598-017-01057-z. PMID:28446777^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Donini S, Ferraris DM, 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. 2017 Apr 26;7(1):1180. doi: 10.1038/s41598-017-01057-z. PMID:28446777 doi:http://dx.doi.org/10.1038/s41598-017-01057-z