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PDBsum entry 1s1f
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Oxidoreductase PDB id
1s1f

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
397 a.a. *
Ligands
HEM-PIM
MLA ×2
GOL
Metals
_HG ×2
Waters ×326
* Residue conservation analysis
PDB id:
1s1f
Name: Oxidoreductase
Title: Crystal structure of streptomyces coelicolor a3(2) cyp158a2 from antibiotic biosynthetic pathways
Structure: Putative cytochrome p450. Chain: a. Synonym: cytochrome p450 cyp158a2. Engineered: yes
Source: Streptomyces coelicolor. Organism_taxid: 100226. Strain: a3(2). Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.50Å     R-factor:   0.202     R-free:   0.216
Authors: B.Zhao,D.C.Lamb,L.Lei,M.Sundaramoorthy,L.M.Podust,M.R.Waterman
Key ref:
B.Zhao et al. (2005). Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2. J Biol Chem, 280, 11599-11607. PubMed id: 15659395 DOI: 10.1074/jbc.M410933200
Date:
06-Jan-04     Release date:   11-Jan-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9FCA6  (C1582_STRCO) -  Biflaviolin synthase CYP158A2 from Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
Seq:
Struc: 		404 a.a.
397 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.14.19.69  - biflaviolin synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. 2 flaviolin + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + H+ = 3,3'-biflaviolin + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 H2O
2. 2 flaviolin + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + H+ = 3,8'-biflaviolin + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 H2O
2 × flaviolin
Bound ligand (Het Group name = PIM)
matches with 44.44% similarity 		+ 2 × reduced [2Fe-2S]-[ferredoxin]
 + O2
 + H(+)
 =
3,3'-biflaviolin
Bound ligand (Het Group name = HEM)
matches with 40.38% similarity 		+ 2 × oxidized [2Fe-2S]-[ferredoxin]
 + 2 × H2O
2 × flaviolin
Bound ligand (Het Group name = PIM)
matches with 44.44% similarity 		+ 2 × reduced [2Fe-2S]-[ferredoxin]
 + O2
 + H(+)
 =
3,8'-biflaviolin
Bound ligand (Het Group name = HEM)
matches with 40.38% similarity 		+ 2 × oxidized [2Fe-2S]-[ferredoxin]
 + 2 × H2O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M410933200 J Biol Chem 280:11599-11607 (2005)
PubMed id: 15659395  
 
 
Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2.
B.Zhao, F.P.Guengerich, A.Bellamine, D.C.Lamb, M.Izumikawa, L.Lei, L.M.Podust, M.Sundaramoorthy, J.A.Kalaitzis, L.M.Reddy, S.L.Kelly, B.S.Moore, D.Stec, M.Voehler, J.R.Falck, T.Shimada, M.R.Waterman.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 7.
FIG. 7. Stereoview of the hydrogen-bonding network among Arg71, Arg288, and Leu293 and ordered waters and the two flaviolin molecules in the CYP158A2 active site. The side chain atoms and flaviolin atoms are rendered as stick figures. Water molecules are displayed as red spheres. Potential hydrogen bonds are dotted green lines. 		Figure 8.
FIG. 8. Proposed diradical mechanism for formation of the flaviolin dimers by CYP158A2.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 11599-11607) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21171581 Y.T.Lee, E.C.Glazer, R.F.Wilson, C.D.Stout, and D.B.Goodin (2011).
Three clusters of conformational States in p450cam reveal a multistep pathway for closing of the substrate access channel .
  Biochemistry, 50, 693-703.  
20097805 D.C.Lamb, L.Lei, B.Zhao, H.Yuan, C.J.Jackson, A.G.Warrilow, T.Skaug, P.J.Dyson, E.S.Dawson, S.L.Kelly, D.L.Hachey, and M.R.Waterman (2010).
Streptomyces coelicolor A3(2) CYP102 protein, a novel fatty acid hydroxylase encoded as a heme domain without an N-terminal redox partner.
  Appl Environ Microbiol, 76, 1975-1980.  
20669042 L.E.Thornton, S.G.Rupasinghe, H.Peng, M.A.Schuler, and M.M.Neff (2010).
Arabidopsis CYP72C1 is an atypical cytochrome P450 that inactivates brassinosteroids.
  Plant Mol Biol, 74, 167-181.  
20446763 T.C.Pochapsky, S.Kazanis, and M.Dang (2010).
Conformational plasticity and structure/function relationships in cytochromes P450.
  Antioxid Redox Signal, 13, 1273-1296.  
20297780 Y.T.Lee, R.F.Wilson, I.Rupniewski, and D.B.Goodin (2010).
P450cam visits an open conformation in the absence of substrate.
  Biochemistry, 49, 3412-3419.
PDB codes: 3l61 3l62 3l63
19555717 I.G.Denisov, D.J.Frank, and S.G.Sligar (2009).
Cooperative properties of cytochromes P450.
  Pharmacol Ther, 124, 151-167.  
19074393 L.H.Xu, S.Fushinobu, H.Ikeda, T.Wakagi, and H.Shoun (2009).
Crystal structures of cytochrome P450 105P1 from Streptomyces avermitilis: conformational flexibility and histidine ligation state.
  J Bacteriol, 191, 1211-1219.
PDB codes: 3e5j 3e5k 3e5l
19416919 P.Belin, M.H.Le Du, A.Fielding, O.Lequin, M.Jacquet, J.B.Charbonnier, A.Lecoq, R.Thai, M.Courçon, C.Masson, C.Dugave, R.Genet, J.L.Pernodet, and M.Gondry (2009).
Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis.
  Proc Natl Acad Sci U S A, 106, 7426-7431.  
19533699 P.F.Widboom, and S.D.Bruner (2009).
Complex oxidation chemistry in the biosynthetic pathways to vancomycin/teicoplanin antibiotics.
  Chembiochem, 10, 1757-1764.  
18677741 A.N.Holding, and J.B.Spencer (2008).
Investigation into the mechanism of phenolic couplings during the biosynthesis of glycopeptide antibiotics.
  Chembiochem, 9, 2209-2214.  
18234666 B.Zhao, X.Lin, L.Lei, D.C.Lamb, S.L.Kelly, M.R.Waterman, and D.E.Cane (2008).
Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor A3(2).
  J Biol Chem, 283, 8183-8189.  
18600471 D.Hamdane, H.Zhang, and P.Hollenberg (2008).
Oxygen activation by cytochrome P450 monooxygenase.
  Photosynth Res, 98, 657-666.  
18622598 E.M.Isin, and F.P.Guengerich (2008).
Substrate binding to cytochromes P450.
  Anal Bioanal Chem, 392, 1019-1030.  
18413310 G.A.Schoch, J.K.Yano, S.Sansen, P.M.Dansette, C.D.Stout, and E.F.Johnson (2008).
Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid.
  J Biol Chem, 283, 17227-17237.
PDB codes: 2nnh 2nni 2nnj 2vn0
18089574 H.Ouellet, L.M.Podust, and P.R.de Montellano (2008).
Mycobacterium tuberculosis CYP130: crystal structure, biophysical characterization, and interactions with antifungal azole drugs.
  J Biol Chem, 283, 5069-5080.
PDB codes: 2uuq 2uvn
18366166 Y.Ding, W.H.Seufert, Z.Q.Beck, and D.H.Sherman (2008).
Analysis of the cryptophycin P450 epoxidase reveals substrate tolerance and cooperativity.
  J Am Chem Soc, 130, 5492-5498.  
18511451 Y.Wada, M.Mitsuda, Y.Ishihara, M.Watanabe, M.Iwasaki, and S.Asahi (2008).
Important amino acid residues that confer CYP2C19 selective activity to CYP2C9.
  J Biochem, 144, 323-333.  
17534532 A.W.Munro, H.M.Girvan, and K.J.McLean (2007).
Variations on a (t)heme--novel mechanisms, redox partners and catalytic functions in the cytochrome P450 superfamily.
  Nat Prod Rep, 24, 585-609.  
17936929 F.P.Guengerich (2007).
Mechanisms of cytochrome P450 substrate oxidation: MiniReview.
  J Biochem Mol Toxicol, 21, 163-168.  
17606921 M.Makino, H.Sugimoto, Y.Shiro, S.Asamizu, H.Onaka, and S.Nagano (2007).
Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton.
  Proc Natl Acad Sci U S A, 104, 11591-11596.
PDB codes: 2z3t 2z3u
  17401212 X.Pang, F.Xu, S.G.Bell, D.Guo, L.L.Wong, and Z.Rao (2007).
Purification, crystallization and preliminary crystallographic analysis of cytochrome P450 203A1 from Rhodopseudomonas palustris.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 342-345.  
16863466 D.C.Lamb, F.P.Guengerich, S.L.Kelly, and M.R.Waterman (2006).
Exploiting Streptomyces coelicolor A3(2) P450s as a model for application in drug discovery.
  Expert Opin Drug Metab Toxicol, 2, 27-40.  
16793528 M.J.de Groot (2006).
Designing better drugs: predicting cytochrome P450 metabolism.
  Drug Discov Today, 11, 601-606.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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