4f4q

Structural highlights

Function

DPRE1_MYCS2 Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans (PubMed:22188377). DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX) (PubMed:22188377). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex (By similarity). Can also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as substrate in vitro (PubMed:22188377, PubMed:22956199). Appears to be essential for the growth of M.smegmatis (PubMed:21346818).[UniProtKB:P9WJF1]^{[1] [2] [3]}

References

1. ↑ Crellin PK, Brammananth R, Coppel RL. Decaprenylphosphoryl-beta-D-ribose 2'-epimerase, the target of benzothiazinones and dinitrobenzamides, is an essential enzyme in Mycobacterium smegmatis. PLoS One. 2011 Feb 8;6(2):e16869. doi: 10.1371/journal.pone.0016869. PMID:21346818 doi:http://dx.doi.org/10.1371/journal.pone.0016869
2. ↑ Trefzer C, Skovierova H, Buroni S, Bobovska A, Nenci S, Molteni E, Pojer F, Pasca MR, Makarov V, Cole ST, Riccardi G, Mikusova K, Johnsson K. Benzothiazinones are suicide inhibitors of mycobacterial decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase DprE1. J Am Chem Soc. 2012 Jan 18;134(2):912-5. doi: 10.1021/ja211042r. Epub 2011 Dec, 21. PMID:22188377 doi:http://dx.doi.org/10.1021/ja211042r
3. ↑ Neres J, Pojer F, Molteni E, Chiarelli LR, Dhar N, Boy-Rottger S, Buroni S, Fullam E, Degiacomi G, Lucarelli AP, Read RJ, Zanoni G, Edmondson DE, De Rossi E, Pasca MR, McKinney JD, Dyson PJ, Riccardi G, Mattevi A, Cole ST, Binda C. Structural Basis for Benzothiazinone-Mediated Killing of Mycobacterium tuberculosis. Sci Transl Med. 2012 Sep 5;4(150):150ra121. PMID:22956199 doi:http://dx.doi.org/10.1126/scitranslmed.3004395