Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin.

Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin.
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DOI:
10.3390/ijms13078500
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发表时间:
2012
影响因子:
5.6
通讯作者:
Lamb DC
Lamb DC
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao B;Moody SC;Hider RC;Lei L;Kelly SL;Waterman MR;Lamb DC

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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.
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