Structural highlights
Function
FRBJ_STRR3 Monooxygenase involved in the biosynthesis of the phosphonate antibiotic FR-33289, an antimalarial agent (PubMed:20142041). Catalyzes the oxidative decarboxylation of the antibiotic FR-900098 (3-(N-acetyl-N-hydroxy)aminopropylphosphonate) to form FR-33289 ((R)-(3-(acetylhydroxyamino)-2-hydroxypropyl)phosphonate) (PubMed:20142041).[1]
Publication Abstract from PubMed
FrbJ is a member of the Fe(2+)/alpha-ketoglutarate-dependent dioxygenase family which hydroxylates the natural product FR-900098 of Streptomyces rubellomurinus, yielding the phosphonate antibiotic FR-33289. Here, the crystal structure of FrbJ, which shows structural homology to taurine dioxygenase (TauD), a key member of the same family, is reported. Unlike other members of the family, FrbJ has an unusual lid structure which consists of two beta-strands with a long loop between them. To investigate the role of this lid motif, a molecular-dynamics simulation was performed with the FrbJ structure. The molecular-dynamics simulation analysis implies that the lid-loop region is highly flexible, which is consistent with the fact that FrbJ has a relatively broad spectrum of substrates with different lengths. Interestingly, an access tunnel is found at the back of the active site which connects the putative binding site of alpha-ketoglutarate to the solvent outside.
Structural analysis of a phosphonate hydroxylase with an access tunnel at the back of the active site.,Li C, Junaid M, Almuqri EA, Hao S, Zhang H Acta Crystallogr F Struct Biol Commun. 2016 May 1;72(Pt 5):362-8. doi:, 10.1107/S2053230X16004933. Epub 2016 Apr 22. PMID:27139827[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Johannes TW, DeSieno MA, Griffin BM, Thomas PM, Kelleher NL, Metcalf WW, Zhao H. Deciphering the late biosynthetic steps of antimalarial compound FR-900098. Chem Biol. 2010 Jan 29;17(1):57-64. PMID:20142041 doi:10.1016/j.chembiol.2009.12.009
- ↑ Li C, Junaid M, Almuqri EA, Hao S, Zhang H. Structural analysis of a phosphonate hydroxylase with an access tunnel at the back of the active site. Acta Crystallogr F Struct Biol Commun. 2016 May 1;72(Pt 5):362-8. doi:, 10.1107/S2053230X16004933. Epub 2016 Apr 22. PMID:27139827 doi:http://dx.doi.org/10.1107/S2053230X16004933
