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Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin
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 cyt...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430247/ https://www.ncbi.nlm.nih.gov/pubmed/22942716 http://dx.doi.org/10.3390/ijms13078500 |
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author | Zhao, Bin Moody, Suzy C. Hider, Robert C. Lei, Li Kelly, Steven L. Waterman, Michael R. Lamb, David C. |
author_facet | Zhao, Bin Moody, Suzy C. Hider, Robert C. Lei, Li Kelly, Steven L. Waterman, Michael R. Lamb, David C. |
author_sort | Zhao, Bin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3430247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-34302472012-08-31 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. Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2012-06-01 /pmc/articles/PMC3430247/ /pubmed/22942716 http://dx.doi.org/10.3390/ijms13078500 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article 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 |
title | Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin |
title_full | Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin |
title_fullStr | Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin |
title_full_unstemmed | Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin |
title_short | Structural Analysis of Cytochrome P450 105N1 Involved in the Biosynthesis of the Zincophore, Coelibactin |
title_sort | structural analysis of cytochrome p450 105n1 involved in the biosynthesis of the zincophore, coelibactin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430247/ https://www.ncbi.nlm.nih.gov/pubmed/22942716 http://dx.doi.org/10.3390/ijms13078500 |
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