4M23

Crystal structure of non-heme iron oxygenase OrfP

Summary for 4M23

• Entry DOI: 10.2210/pdb4m23/pdb
• Related: 4M25 4M26 4M27 4M2C 4M2E 4M2F 4M2G 4M2I 4M2J 4M2K 4M2M
• Descriptor: L-arginine beta-hydroxylase (2 entities in total)
• Functional Keywords: hydroxylase, fe binding, oxidoreductase
• Biological source: Streptomyces lavendulae
• Total number of polymer chains: 4
• Total formula weight: 164752.33

Authors

Chang, C.Y.,Liu, Y.C.,Lyu, S.Y.,Wu, C.C.,Li, T.L. (deposition date: 2013-08-05, release date: 2014-06-18, Last modification date: 2023-11-08)

Primary citation

Chang, C.Y.,Lyu, S.Y.,Liu, Y.C.,Hsu, N.S.,Wu, C.C.,Tang, C.F.,Lin, K.H.,Ho, J.Y.,Wu, C.J.,Tsai, M.D.,Li, T.L.
Biosynthesis of streptolidine involved two unexpected intermediates produced by a dihydroxylase and a cyclase through unusual mechanisms.
Angew.Chem.Int.Ed.Engl., 53:1943-1948, 2014

PubMed Abstract: Streptothricin-F (STT-F), one of the early-discovered antibiotics, consists of three components, a β-lysine homopolymer, an aminosugar D-gulosamine, and an unusual bicyclic streptolidine. The biosynthesis of streptolidine is a long-lasting but unresolved puzzle. Herein, a combination of genetic/biochemical/structural approaches was used to unravel this problem. The STT gene cluster was first sequenced from a Streptomyces variant BCRC 12163, wherein two gene products OrfP and OrfR were characterized in vitro to be a dihydroxylase and a cyclase, respectively. Thirteen high-resolution crystal structures for both enzymes in different reaction intermediate states were snapshotted to help elucidate their catalytic mechanisms. OrfP catalyzes an Fe(II) -dependent double hydroxylation reaction converting L-Arg into (3R,4R)-(OH)2 -L-Arg via (3S)-OH-L-Arg, while OrfR catalyzes an unusual PLP-dependent elimination/addition reaction cyclizing (3R,4R)-(OH)2 -L-Arg to the six-membered (4R)-OH-capreomycidine. The biosynthetic mystery finally comes to light as the latter product was incorporation into STT-F by a feeding experiment.

PubMed: 24505011
DOI: 10.1002/anie.201307989

Experimental method

X-RAY DIFFRACTION (1.76 Å)