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PDBsum entry 1e9x
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Oxidoreductase PDB id
1e9x

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
449 a.a. *
Ligands
HEM-PIM
Waters ×282
* Residue conservation analysis
PDB id:
1e9x
Name: Oxidoreductase
Title: Cytochrome p450 14 alpha-sterol demethylase (cyp51) from mycobacterium tuberculosis in complex with 4-phenylimidazole
Structure: Cytochrome p450 51-like rv0764c. Chain: a. Synonym: cyp51,14alpha-sterol demethylase. Engineered: yes. Mutation: yes. Other_details: cys 394 binds heme iron. 4-phenylimidazole is bound in the active site coordinating heme iron as a sixth ligand
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Cellular_location: cytoplasm. Gene: cyp51 or rv0764c or mtcy369.09c. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.185     R-free:   0.230
Authors: L.M.Podust,T.L.Poulos,M.R.Waterman
Key ref:
L.M.Podust et al. (2001). Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc Natl Acad Sci U S A, 98, 3068-3073. PubMed id: 11248033 DOI: 10.1073/pnas.061562898
Date:
30-Oct-00     Release date:   01-Nov-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P9WPP9  (CP51_MYCTU) -  Sterol 14alpha-demethylase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Seq:
Struc: 		451 a.a.
449 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.14.15.36  - sterol 14alpha-demethylase (ferredoxin).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 14alpha-methyl steroid + 6 reduced [2Fe-2S]-[ferredoxin] + 3 O2 + 5 H+ = a Delta14 steroid + formate + 6 oxidized [2Fe-2S]-[ferredoxin] + 4 H2O
14alpha-methyl steroid
 + 6 × reduced [2Fe-2S]-[ferredoxin]
 + 3 × O2
 + 5 × H(+)
 = Delta(14) steroid
 + formate
 + 6 × oxidized [2Fe-2S]-[ferredoxin]
 + 4 × H2O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.061562898 Proc Natl Acad Sci U S A 98:3068-3073 (2001)
PubMed id: 11248033  
 
 
Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors.
L.M.Podust, T.L.Poulos, M.R.Waterman.
 
  ABSTRACT  
 
Cytochrome P450 14alpha-sterol demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes. CYP51 removes the 14alpha-methyl group from sterol precursors such as lanosterol, obtusifoliol, dihydrolanosterol, and 24(28)-methylene-24,25-dihydrolanosterol. Inhibitors of CYP51 include triazole antifungal agents fluconazole and itraconazole, drugs used in treatment of topical and systemic mycoses. The 2.1- and 2.2-A crystal structures reported here for 4-phenylimidazole- and fluconazole-bound CYP51 from Mycobacterium tuberculosis (MTCYP51) are the first structures of an authentic P450 drug target. MTCYP51 exhibits the P450 fold with the exception of two striking differences-a bent I helix and an open conformation of BC loop-that define an active site-access channel running along the heme plane perpendicular to the direction observed for the substrate entry in P450BM3. Although a channel analogous to that in P450BM3 is evident also in MTCYP51, it is not open at the surface. The presence of two different channels, with one being open to the surface, suggests the possibility of conformationally regulated substrate-in/product-out openings in CYP51. Mapping mutations identified in Candida albicans azole-resistant isolates indicates that azole resistance in fungi develops in protein regions involved in orchestrating passage of CYP51 through different conformational stages along the catalytic cycle rather than in residues directly contacting fluconazole. These new structures provide a basis for rational design of new, more efficacious antifungal agents as well as insight into the molecular mechanism of P450 catalysis.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Ribbon representation of the MTCYP51 structures with the inhibitors bound. Front (A) and top (B) views of the of 4-PI- (yellow) and FLU- (blue) bound MTCYP51 superimposed with an rms deviation of 0.45 Å. Superimpositions for all figures were done by using two-step fitting as implemented in SWISS-PDB VIEWER (33). The first step was performed by using entire structures; for the second step, an rms-deviation cutoff of 1.8 Å was used to select the most structurally homologous regions for subsequent fitting. The second round results in better fitting of the most homologous regions and further divergence of less homologous regions. Heme, red; 4-PI, orange; FLU, light-blue. The I helix is shown also in red. A large cavity of 2,600 Å3, shown in blue, leads from the active site to the molecular surface along the protein domain interface (channel 2). Structural elements significantly deviating among P450 structures are labeled in black, and -sheets that are part of the putative substrate-binding site are labeled in red. All figures, if not otherwise indicated, are generated by using SWISS-PDB VIEWER (33). 		Figure 2.
Fig. 2. Superimposition and alignment of the I helix in known P450 structures. Front (A) and top (B) views of the I helix from superimposed P450 structures assigned in sequence-alignment shown in C. Each structure was superimposed pairwise with MTCYP51 so that rms deviation for the most structurally homologous regions did not exceed 1.2 Å. (C) Alignment of the I helix sequences performed by using BCM SEARCH LAUNCHER (34). Residues identical or homologous in at least half of the compared sequences are shaded in dark or light, respectively. The position of conserved glycine is marked according to MTCYP51 sequence (P77901).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21114623 D.Kim, Y.R.Lim, S.O.Ohk, B.J.Kim, and Y.J.Chun (2011).
Functional expression and characterization of CYP51 from dandruff-causing Malassezia globosa.
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Multiple mechanisms account for resistance to sterol 14α-demethylation inhibitors in field isolates of Mycosphaerella graminicola.
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Synthesis and in vitro antifungal evaluation of 2-(2,4-difluorophenyl)-1-[(1H-indol-3-ylmethyl)methylamino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ols.
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Design, synthesis, and in vitro antifungal activity of 1-[(4-substituted-benzyl)methylamino]-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols.
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21058395 W.Li, J.Shen, G.Liu, Y.Tang, and T.Hoshino (2011).
Exploring coumarin egress channels in human cytochrome P450 2A6 by random acceleration and steered molecular dynamics simulations.
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20625155 A.G.Warrilow, C.M.Martel, J.E.Parker, N.Melo, D.C.Lamb, W.D.Nes, D.E.Kelly, and S.L.Kelly (2010).
Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51).
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19593597 C.Sheng, S.Chen, H.Ji, G.Dong, X.Che, W.Wang, Z.Miao, J.Yao, J.Lü, W.Guo, and W.Zhang (2010).
Evolutionary trace analysis of CYP51 family: implication for site-directed mutagenesis and novel antifungal drug design.
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19923211 G.I.Lepesheva, H.W.Park, T.Y.Hargrove, B.Vanhollebeke, Z.Wawrzak, J.M.Harp, M.Sundaramoorthy, W.D.Nes, E.Pays, M.Chaudhuri, F.Villalta, and M.R.Waterman (2010).
Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implications for selective treatment of human infections.
  J Biol Chem, 285, 1773-1780.
PDB codes: 3g1q 3gw9
20305029 H.J.Cools, J.E.Parker, D.E.Kelly, J.A.Lucas, B.A.Fraaije, and S.L.Kelly (2010).
Heterologous expression of mutated eburicol 14alpha-demethylase (CYP51) proteins of Mycosphaerella graminicola to assess effects on azole fungicide sensitivity and intrinsic protein function.
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19635450 H.Ouellet, J.B.Johnston, and P.R.Ortiz de Montellano (2010).
The Mycobacterium tuberculosis cytochrome P450 system.
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19727863 N.Krishnamoorthy, P.Gajendrarao, S.Thangapandian, Y.Lee, and K.W.Lee (2010).
Probing possible egress channels for multiple ligands in human CYP3A4: a molecular modeling study.
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20446763 T.C.Pochapsky, S.Kazanis, and M.Dang (2010).
Conformational plasticity and structure/function relationships in cytochromes P450.
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18986991 A.J.Powell, J.Tomberg, A.M.Deacon, R.A.Nicholas, and C.Davies (2009).
Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance.
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PDB codes: 3equ 3eqv
19340599 A.S.Planche, M.T.Scotti, A.G.López, V.de Paulo Emerenciano, E.M.Pérez, and E.Uriarte (2009).
Design of novel antituberculosis compounds using graph-theoretical and substructural approaches.
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19190730 C.K.Chen, P.S.Doyle, L.V.Yermalitskaya, Z.B.Mackey, K.K.Ang, J.H.McKerrow, and L.M.Podust (2009).
Trypanosoma cruzi CYP51 Inhibitor Derived from a Mycobacterium tuberculosis Screen Hit.
  PLoS Negl Trop Dis, 3, e372.
PDB codes: 2w09 2w0a 2w0b
19470512 C.Sheng, Z.Miao, H.Ji, J.Yao, W.Wang, X.Che, G.Dong, J.Lü, W.Guo, and W.Zhang (2009).
Three-dimensional model of lanosterol 14 alpha-demethylase from Cryptococcus neoformans: active-site characterization and insights into azole binding.
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19129847 D.Ghosh, J.Griswold, M.Erman, and W.Pangborn (2009).
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PDB code: 3eqm
19015352 E.Lamping, A.Ranchod, K.Nakamura, J.D.Tyndall, K.Niimi, A.R.Holmes, M.Niimi, and R.D.Cannon (2009).
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19418481 G.P.Cañas-Gutiérrez, M.J.Angarita-Velásquez, J.M.Restrepo-Flórez, P.Rodríguez, C.X.Moreno, and R.Arango (2009).
Analysis of the CYP51 gene and encoded protein in propiconazole-resistant isolates of Mycosphaerella fijiensis.
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19146393 H.Ouellet, J.Lang, M.Couture, and P.R.Ortiz de Montellano (2009).
Reaction of Mycobacterium tuberculosis cytochrome P450 enzymes with nitric oxide.
  Biochemistry, 48, 863-872.  
19933331 J.B.Johnston, P.M.Kells, L.M.Podust, and P.R.Ortiz de Montellano (2009).
Biochemical and structural characterization of CYP124: A methyl-branched lipid {omega}-hydroxylase from Mycobacterium tuberculosis.
  Proc Natl Acad Sci U S A, 106, 20687-20692.
PDB codes: 2wm4 2wm5
19074393 L.H.Xu, S.Fushinobu, H.Ikeda, T.Wakagi, and H.Shoun (2009).
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  J Bacteriol, 191, 1211-1219.
PDB codes: 3e5j 3e5k 3e5l
19463001 P.K.Suryadevara, S.Olepu, J.W.Lockman, J.Ohkanda, M.Karimi, C.L.Verlinde, J.M.Kraus, J.Schoepe, W.C.Van Voorhis, A.D.Hamilton, F.S.Buckner, and M.H.Gelb (2009).
Structurally simple inhibitors of lanosterol 14alpha-demethylase are efficacious in a rodent model of acute Chagas disease.
  J Med Chem, 52, 3703-3715.  
17899220 A.Bonifacio, D.Millo, P.H.Keizers, R.Boegschoten, J.N.Commandeur, N.P.Vermeulen, C.Gooijer, and G.van der Zwan (2008).
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18367444 A.N.Eddine, J.P.von Kries, M.V.Podust, T.Warrier, S.H.Kaufmann, and L.M.Podust (2008).
X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51).
  J Biol Chem, 283, 15152-15159.
PDB code: 2vku
18853217 A.Warrilow, C.Ugochukwu, D.Lamb, D.Kelly, and S.Kelly (2008).
Expression and Characterization of CYP51, the Ancient Sterol 14-demethylase Activity for Cytochromes P450 (CYP), in the White-Rot Fungus Phanerochaete chrysosporium.
  Lipids, 43, 1143-1153.  
19053752 C.C.Peng, J.L.Cape, T.Rushmore, G.J.Crouch, and J.P.Jones (2008).
Cytochrome P450 2C9 type II binding studies on quinoline-4-carboxamide analogues.
  J Med Chem, 51, 8000-8011.  
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
18818197 K.J.McLean, P.Carroll, D.G.Lewis, A.J.Dunford, H.E.Seward, R.Neeli, M.R.Cheesman, L.Marsollier, P.Douglas, W.E.Smith, I.Rosenkrands, S.T.Cole, D.Leys, T.Parish, and A.W.Munro (2008).
Characterization of active site structure in CYP121. A cytochrome P450 essential for viability of Mycobacterium tuberculosis H37Rv.
  J Biol Chem, 283, 33406-33416.
PDB code: 3cxv
18444894 L.G.Dover, A.Bhatt, V.Bhowruth, B.E.Willcox, and G.S.Besra (2008).
New drugs and vaccines for drug-resistant Mycobacterium tuberculosis infections.
  Expert Rev Vaccines, 7, 481-497.  
18787124 L.Li, Z.Chang, Z.Pan, Z.Q.Fu, and X.Wang (2008).
Modes of heme binding and substrate access for cytochrome P450 CYP74A revealed by crystal structures of allene oxide synthase.
  Proc Natl Acad Sci U S A, 105, 13883-13888.
PDB codes: 3dam 3dan 3dbm
17964172 T.Korosec, J.Acimovic, M.Seliskar, D.Kocjan, K.F.Tacer, D.Rozman, and U.Urleb (2008).
Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14alpha-demethylase (CYP51).
  Bioorg Med Chem, 16, 209-221.  
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.  
16963187 G.I.Lepesheva, and M.R.Waterman (2007).
Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms.
  Biochim Biophys Acta, 1770, 467-477.  
17585868 G.I.Lepesheva, M.Seliskar, C.G.Knutson, N.V.Stourman, D.Rozman, and M.R.Waterman (2007).
Conformational dynamics in the F/G segment of CYP51 from Mycobacterium tuberculosis monitored by FRET.
  Arch Biochem Biophys, 464, 221-227.  
17846131 L.M.Podust, J.P.von Kries, A.N.Eddine, Y.Kim, L.V.Yermalitskaya, R.Kuehne, H.Ouellet, T.Warrier, M.Alteköster, J.S.Lee, J.Rademann, H.Oschkinat, S.H.Kaufmann, and M.R.Waterman (2007).
Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography.
  Antimicrob Agents Chemother, 51, 3915-3923.
PDB codes: 2bz9 2ci0 2cib
17986082 L.Zhao, D.Liu, Q.Zhang, S.Zhang, J.Wan, and W.Xiao (2007).
Expression and homology modeling of sterol 14alpha-demethylase from Penicillium digitatum.
  FEMS Microbiol Lett, 277, 37-43.  
17270273 R.L.Haining, and M.Nichols-Haining (2007).
Cytochrome P450-catalyzed pathways in human brain: metabolism meets pharmacology or old drugs with new mechanism of action?
  Pharmacol Ther, 113, 537-545.  
18005930 S.G.Rupasinghe, H.Duan, H.L.Frericks Schmidt, D.A.Berthold, C.M.Rienstra, and M.A.Schuler (2007).
High-yield expression and purification of isotopically labeled cytochrome P450 monooxygenases for solid-state NMR spectroscopy.
  Biochim Biophys Acta, 1768, 3061-3070.  
17603162 S.H.Chen, C.Q.Sheng, X.H.Xu, Y.Y.Jiang, W.N.Zhang, and C.He (2007).
Identification of Y118 amino acid residue in Candida albicans sterol 14alpha-demethylase associated with the enzyme activity and selective antifungal activity of azole analogues.
  Biol Pharm Bull, 30, 1246-1253.  
17630911 V.V.Shumyantseva, T.V.Bulko, G.P.Kuznetsova, A.V.Lisitsa, E.A.Ponomarenko, I.I.Karuzina, and A.I.Archakov (2007).
Electrochemical reduction of sterol-14alpha-demethylase from Mycobacterium tuberculosis (CYP51b1).
  Biochemistry (Mosc), 72, 658-663.  
17726049 Y.Chérasse, A.C.Maurin, C.Chaveroux, C.Jousse, V.Carraro, L.Parry, C.Deval, C.Chambon, P.Fafournoux, and A.Bruhat (2007).
The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP.
  Nucleic Acids Res, 35, 5954-5965.  
16482386 C.Imbert, S.Imbert-Bouyer, C.Kauffmann-Lacroix, G.Daniault, and M.H.Rodier (2006).
Effect of azoles on the secretion of a Candida albicans metallopeptidase.
  Mycopathologia, 161, 147-152.  
17020766 C.W.Chiang, H.C.Yeh, L.H.Wang, and N.L.Chan (2006).
Crystal structure of the human prostacyclin synthase.
  J Mol Biol, 364, 266-274.
PDB code: 2iag
16500955 D.E.Prosser, Y.Guo, Z.Jia, and G.Jones (2006).
Structural motif-based homology modeling of CYP27A1 and site-directed mutational analyses affecting vitamin D hydroxylation.
  Biophys J, 90, 3389-3409.  
16872679 I.A.Pikuleva (2006).
Cytochrome P450s and cholesterol homeostasis.
  Pharmacol Ther, 112, 761-773.  
16989119 I.Accoceberry, and T.Noël (2006).
[Antifungals cellular targets and mechanisms of resistance]
  Therapie, 61, 195-199.  
16700545 J.T.Pearson, J.J.Hill, J.Swank, N.Isoherranen, K.L.Kunze, and W.M.Atkins (2006).
Surface plasmon resonance analysis of antifungal azoles binding to CYP3A4 with kinetic resolution of multiple binding orientations.
  Biochemistry, 45, 6341-6353.  
16581251 K.J.McLean, D.Clift, D.G.Lewis, M.Sabri, P.R.Balding, M.J.Sutcliffe, D.Leys, and A.W.Munro (2006).
The preponderance of P450s in the Mycobacterium tuberculosis genome.
  Trends Microbiol, 14, 220-228.  
16793528 M.J.de Groot (2006).
Designing better drugs: predicting cytochrome P450 metabolism.
  Drug Discov Today, 11, 601-606.  
  16543605 M.P.Pietila, P.K.Vohra, B.Sanyal, N.L.Wengenack, S.Raghavakaimal, and C.F.Thomas (2006).
Cloning and characterization of CYP51 from Mycobacterium avium.
  Am J Respir Cell Mol Biol, 35, 236-242.  
17009958 N.V.Strushkevich, I.N.Harnastai, G.I.Lepesheva, and S.A.Usanov (2006).
Role of C-terminal sequence of cytochrome P450scc in folding and functional activity.
  Biochemistry (Mosc), 71, 1027-1034.  
16754609 R.E.Summons, A.S.Bradley, L.L.Jahnke, and J.R.Waldbauer (2006).
Steroids, triterpenoids and molecular oxygen.
  Philos Trans R Soc Lond B Biol Sci, 361, 951-968.  
17124172 X.Qi, S.Bakht, B.Qin, M.Leggett, A.Hemmings, F.Mellon, J.Eagles, D.Werck-Reichhart, H.Schaller, A.Lesot, R.Melton, and A.Osbourn (2006).
A different function for a member of an ancient and highly conserved cytochrome P450 family: from essential sterols to plant defense.
  Proc Natl Acad Sci U S A, 103, 18848-18853.  
16059669 B.Rupp, S.Raub, C.Marian, and H.D.Höltje (2005).
Molecular design of two sterol 14alpha-demethylase homology models and their interactions with the azole antifungals ketoconazole and bifonazole.
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16289312 F.Bouvier, A.Rahier, and B.Camara (2005).
Biogenesis, molecular regulation and function of plant isoprenoids.
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15770070 H.Yasui, S.Hayashi, and H.Sakurai (2005).
Possible involvement of singlet oxygen species as multiple oxidants in p450 catalytic reactions.
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16258319 J.A.van Burik (2005).
Role of new antifungal agents in prophylaxis of mycoses in high risk patients.
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15617063 J.Mestres (2005).
Structure conservation in cytochromes P450.
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15855504 R.A.Helmick, A.E.Fletcher, A.M.Gardner, C.R.Gessner, A.N.Hvitved, M.C.Gustin, and P.R.Gardner (2005).
Imidazole antibiotics inhibit the nitric oxide dioxygenase function of microbial flavohemoglobin.
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15651036 S.B.Kirton, C.W.Murray, M.L.Verdonk, and R.D.Taylor (2005).
Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins.
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16201925 S.Park, and D.S.Perlin (2005).
Establishing surrogate markers for fluconazole resistance in Candida albicans.
  Microb Drug Resist, 11, 232-238.  
15215142 E.Mellado, G.Garcia-Effron, L.Alcazar-Fuoli, M.Cuenca-Estrella, and J.L.Rodriguez-Tudela (2004).
Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs.
  Antimicrob Agents Chemother, 48, 2747-2750.  
14742211 L.Xiao, V.Madison, A.S.Chau, D.Loebenberg, R.E.Palermo, and P.M.McNicholas (2004).
Three-dimensional models of wild-type and mutated forms of cytochrome P450 14alpha-sterol demethylases from Aspergillus fumigatus and Candida albicans provide insights into posaconazole binding.
  Antimicrob Agents Chemother, 48, 568-574.  
15377227 P.Benveniste (2004).
Biosynthesis and accumulation of sterols.
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12709346 A.M.Nascimento, G.H.Goldman, S.Park, S.A.Marras, G.Delmas, U.Oza, K.Lolans, M.N.Dudley, P.A.Mann, and D.S.Perlin (2003).
Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole.
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14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12831319 D.F.Lewis (2003).
P450 structures and oxidative metabolism of xenobiotics.
  Pharmacogenomics, 4, 387-395.  
14563924 E.E.Scott, Y.A.He, M.R.Wester, M.A.White, C.C.Chin, J.R.Halpert, E.F.Johnson, and C.D.Stout (2003).
An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution.
  Proc Natl Acad Sci U S A, 100, 13196-13201.
PDB code: 1po5
14657358 F.Buckner, K.Yokoyama, J.Lockman, K.Aikenhead, J.Ohkanda, M.Sadilek, S.Sebti, W.Van Voorhis, A.Hamilton, and M.H.Gelb (2003).
A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents.
  Proc Natl Acad Sci U S A, 100, 15149-15153.  
12823944 F.C.Odds, A.J.Brown, and N.A.Gow (2003).
Antifungal agents: mechanisms of action.
  Trends Microbiol, 11, 272-279.  
  12611652 J.A.Zarn, B.J.Brüschweiler, and J.R.Schlatter (2003).
Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alpha-demethylase and aromatase.
  Environ Health Perspect, 111, 255-261.  
14503006 M.A.Schuler, and D.Werck-Reichhart (2003).
Functional genomics of P450s.
  Annu Rev Plant Biol, 54, 629-667.  
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
12861225 P.A.Williams, J.Cosme, A.Ward, H.C.Angove, D.Matak Vinković, and H.Jhoti (2003).
Crystal structure of human cytochrome P450 2C9 with bound warfarin.
  Nature, 424, 464-468.
PDB codes: 1og2 1og5
14661979 S.Izumi, H.Kaneko, T.Yamazaki, T.Hirata, and S.Kominami (2003).
Membrane topology of guinea pig cytochrome P450 17 alpha revealed by a combination of chemical modifications and mass spectrometry.
  Biochemistry, 42, 14663-14669.  
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
12654649 T.Fukuoka, D.A.Johnston, C.A.Winslow, M.J.de Groot, C.Burt, C.A.Hitchcock, and S.G.Filler (2003).
Genetic basis for differential activities of fluconazole and voriconazole against Candida krusei.
  Antimicrob Agents Chemother, 47, 1213-1219.  
14597705 T.L.Poulos (2003).
Cytochrome P450 flexibility.
  Proc Natl Acad Sci U S A, 100, 13121-13122.  
11914502 C.G.Mowat, D.Leys, K.J.McLean, S.L.Rivers, A.Richmond, A.W.Munro, M.Ortiz Lombardia, P.M.Alzari, G.A.Reid, S.K.Chapman, and M.D.Walkinshaw (2002).
Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis.
  Acta Crystallogr D Biol Crystallogr, 58, 704-705.  
11901654 D.Sanglard, and F.C.Odds (2002).
Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences.
  Lancet Infect Dis, 2, 73-85.  
12160856 D.Sanglard (2002).
Resistance of human fungal pathogens to antifungal drugs.
  Curr Opin Microbiol, 5, 379-385.  
12617470 G.F.Gibbons (2002).
The role of cytochrome P450 in the regulation of cholesterol biosynthesis.
  Lipids, 37, 1163-1170.  
11922953 M.J.de Groot, and S.Ekins (2002).
Pharmacophore modeling of cytochromes P450.
  Adv Drug Deliv Rev, 54, 367-383.  
11959989 P.J.Winn, S.K.Lüdemann, R.Gauges, V.Lounnas, and R.C.Wade (2002).
Comparison of the dynamics of substrate access channels in three cytochrome P450s reveals different opening mechanisms and a novel functional role for a buried arginine.
  Proc Natl Acad Sci U S A, 99, 5361-5366.  
12482514 V.Urlacher, and R.D.Schmid (2002).
Biotransformations using prokaryotic P450 monooxygenases.
  Curr Opin Biotechnol, 13, 557-564.  
12207646 Y.Sawada, K.Kinoshita, T.Akashi, T.Aoki, and S.Ayabe (2002).
Key amino acid residues required for aryl migration catalysed by the cytochrome P450 2-hydroxyisoflavanone synthase.
  Plant J, 31, 555-564.  
11606730 A.R.Dunn, I.J.Dmochowski, A.M.Bilwes, H.B.Gray, and B.R.Crane (2001).
Probing the open state of cytochrome P450cam with ruthenium-linker substrates.
  Proc Natl Acad Sci U S A, 98, 12420-12425.
PDB code: 1k2o
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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