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Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin
Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA
Institute of Life Science, Medical School, Swansea University, Singleton Park, Swansea, SA2 8PP, UK
Institute of Pharmaceutical Science, King’s College London, 5th Floor, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
* Authors to whom correspondence should be addressed.
Received: 1 June 2012; in revised form: 22 June 2012 / Accepted: 28 June 2012 / Published: 9 July 2012
Abstract: Coelibactin is a putative non-ribosomally synthesized peptide with predicted zincophore activity and which has been implicated in antibiotic regulation in Streptomyces coelicolor A3(2). The coelibactin biosynthetic pathway contains a stereo- and regio-specific monooxygenation step catalyzed by a cytochrome P450 enzyme (CYP105N1). We have determined the X-ray crystal structure of CYP105N1 at 2.9 Å and analyzed it in the context of the bacterial CYP105 family as a whole. The crystal structure reveals a channel between the α-helical domain and the β-sheet domain exposing the heme pocket and the long helix I to the solvent. This wide-open conformation of CYP105N1 may be related to the bulky substrate coelibactin. The ligand-free CYP105N1 structure has enough room in the substrate access channel to allow the coelibactin to enter into the active site. Analysis of typical siderophore ligands suggests that CYP105N1 may produce derivatives of coelibactin, which would then be able to chelate the zinc divalent cation.
Keywords: cytochrome P450; CYP105N1; siderophore; Streptomyces coelicolor A3(2); zinc chelation
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Zhao, B.; Moody, S.C.; Hider, R.C.; Lei, L.; Kelly, S.L.; Waterman, M.R.; Lamb, D.C. Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin. Int. J. Mol. Sci. 2012, 13, 8500-8513.
Zhao B, Moody SC, Hider RC, Lei L, Kelly SL, Waterman MR, Lamb DC. Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin. International Journal of Molecular Sciences. 2012; 13(7):8500-8513.
Zhao, Bin; Moody, Suzy C.; Hider, Robert C.; Lei, Li; Kelly, Steven L.; Waterman, Michael R.; Lamb, David C. 2012. "Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin." Int. J. Mol. Sci. 13, no. 7: 8500-8513.