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

Bin Zhao, Suzy C Moody, Robert C Hider, Li Lei, Steven L Kelly, Michael R Waterman, David C Lamb

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)8500-13
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume13
Issue number7
DOIs
Publication statusPublished - 2012

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biosynthesis
cytochromes
Biosynthesis
structural analysis
Structural analysis
Cytochrome P-450 Enzyme System
Crystal structure
Ligands
ligands
crystal structure
antibiotics
Antibiotics
Substrates
chelates
helices
Peptides
peptides
rooms
Conformations
enzymes

Cite this

Zhao, Bin ; Moody, Suzy C ; Hider, Robert C ; Lei, Li ; Kelly, Steven L ; Waterman, Michael R ; Lamb, David C. / Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin. In: International Journal of Molecular Sciences. 2012 ; Vol. 13, No. 7. pp. 8500-13.
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title = "Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin",
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 {\AA} 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.",
author = "Bin Zhao and Moody, {Suzy C} and Hider, {Robert C} and Li Lei and Kelly, {Steven L} and Waterman, {Michael R} and Lamb, {David C}",
year = "2012",
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Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin. / Zhao, Bin; Moody, Suzy C; Hider, Robert C; Lei, Li; Kelly, Steven L; Waterman, Michael R; Lamb, David C.

In: International Journal of Molecular Sciences, Vol. 13, No. 7, 2012, p. 8500-13.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin

AU - Zhao, Bin

AU - Moody, Suzy C

AU - Hider, Robert C

AU - Lei, Li

AU - Kelly, Steven L

AU - Waterman, Michael R

AU - Lamb, David C

PY - 2012

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AB - 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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DO - 10.3390/ijms13078500

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