1se6
From Proteopedia
(New page: 200px<br /><applet load="1se6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1se6, resolution 1.75Å" /> '''Crystal Structure of...) |
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| - | [[Image:1se6.gif|left|200px]]<br /><applet load="1se6" size=" | + | [[Image:1se6.gif|left|200px]]<br /><applet load="1se6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1se6, resolution 1.75Å" /> | caption="1se6, resolution 1.75Å" /> | ||
'''Crystal Structure of Streptomyces Coelicolor A3(2) CYP158A2 from antibiotic biosynthetic pathways'''<br /> | '''Crystal Structure of Streptomyces Coelicolor A3(2) CYP158A2 from antibiotic biosynthetic pathways'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cytochrome P450 158A2 (CYP158A2) is encoded within a three-gene operon | + | Cytochrome P450 158A2 (CYP158A2) is encoded within a three-gene operon (sco1206-sco1208) in the prototypic soil bacterium Streptomyces coelicolor A3(2). This operon is widely conserved among streptomycetes. CYP158A2 has been suggested to produce polymers of flaviolin, a pigment that may protect microbes from UV radiation, in combination with the adjacent rppA gene, which encodes the type III polyketide synthase, 1,3,6,8-tetrahydroxynaphthalene synthase. Following cloning, expression, and purification of this cytochrome P450, we have shown that it can produce dimer and trimer products from the substrate flaviolin and that the structures of two of the dimeric products were established using mass spectrometry and multiple NMR methods. A comparison of the x-ray structures of ligand-free (1.75 angstroms) and flaviolin-bound (1.62 angstroms) forms of CYP158A2 demonstrates a major conformational change upon ligand binding that closes the entry into the active site, partly due to repositioning of the F and G helices. Particularly interesting is the presence of two molecules of flaviolin in the closed active site. The flaviolin molecules form a quasi-planar three-molecule stack including the heme of CYP158A2, suggesting that oxidative C-C coupling of these phenolic molecules leads to the production of flaviolin dimers. |
==About this Structure== | ==About this Structure== | ||
| - | 1SE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacteria Bacteria] with SPK, HEM and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1SE6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacteria Bacteria] with <scene name='pdbligand=SPK:'>SPK</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SE6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bacteria]] | [[Category: Bacteria]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Lamb, D | + | [[Category: Lamb, D C.]] |
[[Category: Lei, L.]] | [[Category: Lei, L.]] | ||
| - | [[Category: Podust, L | + | [[Category: Podust, L M.]] |
[[Category: Sundaramoorthy, M.]] | [[Category: Sundaramoorthy, M.]] | ||
| - | [[Category: Waterman, M | + | [[Category: Waterman, M R.]] |
[[Category: Zhao, B.]] | [[Category: Zhao, B.]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: streptomyces]] | [[Category: streptomyces]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:36 2008'' |
Revision as of 13:00, 21 February 2008
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Crystal Structure of Streptomyces Coelicolor A3(2) CYP158A2 from antibiotic biosynthetic pathways
Overview
Cytochrome P450 158A2 (CYP158A2) is encoded within a three-gene operon (sco1206-sco1208) in the prototypic soil bacterium Streptomyces coelicolor A3(2). This operon is widely conserved among streptomycetes. CYP158A2 has been suggested to produce polymers of flaviolin, a pigment that may protect microbes from UV radiation, in combination with the adjacent rppA gene, which encodes the type III polyketide synthase, 1,3,6,8-tetrahydroxynaphthalene synthase. Following cloning, expression, and purification of this cytochrome P450, we have shown that it can produce dimer and trimer products from the substrate flaviolin and that the structures of two of the dimeric products were established using mass spectrometry and multiple NMR methods. A comparison of the x-ray structures of ligand-free (1.75 angstroms) and flaviolin-bound (1.62 angstroms) forms of CYP158A2 demonstrates a major conformational change upon ligand binding that closes the entry into the active site, partly due to repositioning of the F and G helices. Particularly interesting is the presence of two molecules of flaviolin in the closed active site. The flaviolin molecules form a quasi-planar three-molecule stack including the heme of CYP158A2, suggesting that oxidative C-C coupling of these phenolic molecules leads to the production of flaviolin dimers.
About this Structure
1SE6 is a Single protein structure of sequence from Bacteria with , and as ligands. Full crystallographic information is available from OCA.
Reference
Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2., Zhao B, Guengerich FP, Bellamine A, Lamb DC, Izumikawa M, Lei L, Podust LM, Sundaramoorthy M, Kalaitzis JA, Reddy LM, Kelly SL, Moore BS, Stec D, Voehler M, Falck JR, Shimada T, Waterman MR, J Biol Chem. 2005 Mar 25;280(12):11599-607. Epub 2005 Jan 19. PMID:15659395
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