Structural highlights
Publication Abstract from PubMed
The indolocarbazole biosynthetic enzymes StaC, InkE, RebC, and AtmC mediate the degree of oxidation of chromopyrrolic acid on route to the natural products staurosporine, K252a, rebeccamycin, and AT2433-A1, respectively. Here, we show that StaC and InkE, which mediate a net 4-electron oxidation, bind FAD with a micromolar K(d), whereas RebC and AtmC, which mediate a net 8-electron oxidation, bind FAD with a nanomolar K(d) while displaying the same FAD redox properties. We further create RebC-10x, a RebC protein with ten StaC-like amino acid substitutions outside of previously characterized FAD-binding motifs and the complementary StaC-10x. We find that these mutations mediate both FAD affinity and product specificity, with RebC-10x displaying higher StaC activity than StaC itself. X-ray structures of this StaC catalyst identify the substrate of StaC as 7-carboxy-K252c and suggest a unique mechanism for this FAD-dependent enzyme.
An Unusual Role for a Mobile Flavin in StaC-like Indolocarbazole Biosynthetic Enzymes.,Goldman PJ, Ryan KS, Hamill MJ, Howard-Jones AR, Walsh CT, Elliott SJ, Drennan CL Chem Biol. 2012 Jul 27;19(7):855-65. PMID:22840773[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Goldman PJ, Ryan KS, Hamill MJ, Howard-Jones AR, Walsh CT, Elliott SJ, Drennan CL. An Unusual Role for a Mobile Flavin in StaC-like Indolocarbazole Biosynthetic Enzymes. Chem Biol. 2012 Jul 27;19(7):855-65. PMID:22840773 doi:10.1016/j.chembiol.2012.05.016
