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PDBsum entry 1w0f

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Oxidoreductase PDB id
1w0f
Jmol
Contents
Protein chain
459 a.a. *
Ligands
STR
HEM
Waters ×47
* Residue conservation analysis
PDB id:
1w0f
Name: Oxidoreductase
Title: Crystal structure of human cytochrome p450 3a4
Structure: Cytochrome p450 3a4. Chain: a. Fragment: soluble domain, residues 24-502. Synonym: quinine 3-monooxygenase, cypiiia4, nifedipine oxidase, nf-25, p450-pcn1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.65Å     R-factor:   0.239     R-free:   0.303
Authors: P.A.Williams,J.Cosme,D.M.Vinkovic,A.Ward,H.C.Angove,P.J.Day, C.Vonrhein,I.J.Tickle,H.Jhoti
Key ref:
P.A.Williams et al. (2004). Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science, 305, 683-686. PubMed id: 15256616 DOI: 10.1126/science.1099736
Date:
03-Jun-04     Release date:   22-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08684  (CP3A4_HUMAN) -  Cytochrome P450 3A4
Seq:
Struc:
503 a.a.
459 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.1.14.13.157  - 1,8-cineole 2-exo-monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 1,8-cineole + NADPH + O2 = 2-exo-hydroxy-1,8-cineole + NADP+ + H2O
1,8-cineole
+ NADPH
+ O(2)
= 2-exo-hydroxy-1,8-cineole
+ NADP(+)
+ H(2)O
      Cofactor: Heme-thiolate
   Enzyme class 2: E.C.1.14.13.32  - Albendazole monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Albendazole + NADPH + O2 = albendazole S-oxide + NADP+ + H2O
Albendazole
Bound ligand (Het Group name = STR)
matches with 74.00% similarity
+ NADPH
+ O(2)
= albendazole S-oxide
+ NADP(+)
+ H(2)O
      Cofactor: FAD
FAD
   Enzyme class 3: E.C.1.14.13.67  - Quinine 3-monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Quinine + NADPH + O2 = 3-hydroxyquinine + NADP+ + H2O
Quinine
+ NADPH
+ O(2)
=
3-hydroxyquinine
Bound ligand (Het Group name = HEM)
matches with 52.00% similarity
+ NADP(+)
+ H(2)O
      Cofactor: Heme-thiolate
   Enzyme class 4: E.C.1.14.13.97  - Taurochenodeoxycholate 6-alpha-hydroxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. Taurochenodeoxycholate + NADPH + O2 = taurohyocholate + NADP+ + H2O
2. Lithocholate + NADPH + O2 = hyodeoxycholate + NADP+ + H2O
Taurochenodeoxycholate
+ NADPH
+ O(2)
= taurohyocholate
+ NADP(+)
+ H(2)O
Lithocholate
+ NADPH
+ O(2)
= hyodeoxycholate
+ NADP(+)
+ H(2)O
      Cofactor: Heme-thiolate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   7 terms 
  Biological process     lipid metabolic process   16 terms 
  Biochemical function     oxidoreductase activity     18 terms  

 

 
    reference    
 
 
DOI no: 10.1126/science.1099736 Science 305:683-686 (2004)
PubMed id: 15256616  
 
 
Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone.
P.A.Williams, J.Cosme, D.M.Vinkovic, A.Ward, H.C.Angove, P.J.Day, C.Vonrhein, I.J.Tickle, H.Jhoti.
 
  ABSTRACT  
 
Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Stereoimage showing the structural overlay of CYP3A4 in red, with P450 BM3 (molecule A of PDB entry 1BU7 [PDB] ) in blue, and P450 EryF (PDB entry 1OXA [PDB] ) in yellow. The heme is depicted as a ball-and-stick model toward the bottom of the figure. The F helix of CYP3A4 (red) is notably shorter than the F helices of P450 BM3 (blue) or P450 EryF (yellow). CYP3A4 has two helices F' and G' that are absent in P450 BM3, P450 EryF, and other bacterial P450 structures.
Figure 4.
Fig. 4. Peripheral binding of progesterone to CYP3A4. The solvent-accessible surface of the progesterone molecule is shown in yellow at the top of the figure. A cross section of the solvent-accessible surface of CYP3A4 is shown in blue, revealing the active-site cavity of CYP3A4 in the center of the figure. Progesterone sits in a shallow pocket on top of the Phe-cluster of CYP3A4, separated from the heme by the F-G region of the molecule. Progesterone binds 17 Å above the heme iron and on the face of CYP3A4 most likely to interact with the membrane.
 
  The above figures are reprinted by permission from the AAAs: Science (2004, 305, 683-686) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20857167 D.Degregorio, S.J.Sadeghi, G.Di Nardo, G.Gilardi, and S.P.Solinas (2011).
Understanding uncoupling in the multiredox centre P450 3A4-BMR model system.
  J Biol Inorg Chem, 16, 109-116.  
21395496 D.R.Davydov (2011).
Microsomal monooxygenase as a multienzyme system: the role of P450-P450 interactions.
  Expert Opin Drug Metab Toxicol, 7, 543-558.  
  21143007 H.Fernando, J.A.Rumfeldt, N.Y.Davydova, J.R.Halpert, and D.R.Davydov (2011).
Multiple substrate-binding sites are retained in cytochrome P450 3A4 mutants with decreased cooperativity.
  Xenobiotica, 41, 281-289.  
20851588 K.A.Salminen, A.Meyer, L.Jerabkova, L.E.Korhonen, M.Rahnasto, R.O.Juvonen, P.Imming, and H.Raunio (2011).
Inhibition of human drug metabolizing cytochrome P450 enzymes by plant isoquinoline alkaloids.
  Phytomedicine, 18, 533-538.  
21154803 M.Ma, S.G.Bell, W.Yang, Y.Hao, N.H.Rees, M.Bartlam, W.Zhou, L.L.Wong, and Z.Rao (2011).
Structural Analysis of CYP101C1 from Novosphingobium aromaticivorans DSM12444.
  Chembiochem, 12, 88-99.
PDB codes: 3oft 3ofu
20863320 M.Yao, M.Dai, Z.Liu, L.Huang, D.Chen, Y.Wang, D.Peng, X.Wang, Z.Liu, and Z.Yuan (2011).
Comparison of the substrate kinetics of pig CYP3A29 with pig liver microsomes and human CYP3A4.
  Biosci Rep, 31, 211-220.  
21372830 P.P.Dong, Z.Z.Fang, Y.Y.Zhang, G.B.Ge, Y.X.Mao, L.L.Zhu, Y.Q.Qu, W.Li, L.M.Wang, C.X.Liu, and L.Yang (2011).
Substrate-dependent modulation of the catalytic activity of CYP3A by erlotinib.
  Acta Pharmacol Sin, 32, 399-407.  
  21117944 Y.H.Liu, S.L.Mo, H.C.Bi, B.F.Hu, C.G.Li, Y.T.Wang, L.Huang, M.Huang, W.Duan, J.P.Liu, M.Q.Wei, and S.F.Zhou (2011).
Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study.
  Xenobiotica, 41, 259-280.  
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.  
19961857 A.J.Annalora, D.B.Goodin, W.X.Hong, Q.Zhang, E.F.Johnson, and C.D.Stout (2010).
Crystal structure of CYP24A1, a mitochondrial cytochrome P450 involved in vitamin D metabolism.
  J Mol Biol, 396, 441-451.
PDB codes: 3k9v 3k9y
21070279 A.Schmitz, S.Demmel, L.M.Peters, T.Leeb, M.Mevissen, and B.Haase (2010).
Comparative human-horse sequence analysis of the CYP3A subfamily gene cluster.
  Anim Genet, 41, 72-79.  
20387782 D.Fishelovitch, S.Shaik, H.J.Wolfson, and R.Nussinov (2010).
How does the reductase help to regulate the catalytic cycle of cytochrome P450 3A4 using the conserved water channel?
  J Phys Chem B, 114, 5964-5970.  
19808095 D.Ghosh, J.Griswold, M.Erman, and W.Pangborn (2010).
X-ray structure of human aromatase reveals an androgen-specific active site.
  J Steroid Biochem Mol Biol, 118, 197-202.  
19878193 H.Sun, and D.O.Scott (2010).
Structure-based drug metabolism predictions for drug design.
  Chem Biol Drug Des, 75, 3.  
20937904 I.F.Sevrioukova, and T.L.Poulos (2010).
Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir.
  Proc Natl Acad Sci U S A, 107, 18422-18427.
PDB code: 3nxu
21170327 J.Yan, and Z.Cai (2010).
Molecular evolution and functional divergence of the cytochrome P450 3 (CYP3) Family in Actinopterygii (ray-finned fish).
  PLoS One, 5, e14276.  
20498847 K.M.Manoj, A.Baburaj, B.Ephraim, F.Pappachan, P.P.Maviliparambathu, U.K.Vijayan, S.V.Narayanan, K.Periasamy, E.A.George, and L.T.Mathew (2010).
Explaining the atypical reaction profiles of heme enzymes with a novel mechanistic hypothesis and kinetic treatment.
  PLoS One, 5, e10601.  
20033806 N.Hanioka, M.Yamamoto, T.Tanaka-Kagawa, H.Jinno, and S.Narimatsu (2010).
Functional characterization of human cytochrome P4502E1 allelic variants: in vitro metabolism of benzene and toluene by recombinant enzymes expressed in yeast cells.
  Arch Toxicol, 84, 363-371.  
19819902 N.Kasai, S.Ikushiro, S.Hirosue, A.Arisawa, H.Ichinose, Y.Uchida, H.Wariishi, M.Ohta, and T.Sakaki (2010).
Atypical kinetics of cytochromes P450 catalysing 3'-hydroxylation of flavone from the white-rot fungus Phanerochaete chrysosporium.
  J Biochem, 147, 117-125.  
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.
  J Mol Model, 16, 607-614.  
20579289 N.Osada, Y.Uno, K.Mineta, Y.Kameoka, I.Takahashi, and K.Terao (2010).
Ancient genome-wide admixture extends beyond the current hybrid zone between Macaca fascicularis and M. mulatta.
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20361239 R.J.Unwalla, J.B.Cross, S.Salaniwal, A.D.Shilling, L.Leung, J.Kao, and C.Humblet (2010).
Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism.
  J Comput Aided Mol Des, 24, 237-256.  
20583201 R.T.Jones, S.E.Bakker, D.Stone, S.N.Shuttleworth, S.Boundy, C.McCart, P.J.Daborn, R.H.ffrench-Constant, and J.M.van den Elsen (2010).
Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance.
  Pest Manag Sci, 66, 1106-1115.  
20697309 V.Agrawal, J.H.Choi, K.M.Giacomini, and W.L.Miller (2010).
Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase.
  Pharmacogenet Genomics, 20, 611-618.  
20879989 Y.Farooq, and G.C.Roberts (2010).
Kinetics of electron transfer between NADPH-cytochrome P450 reductase and cytochrome P450 3A4.
  Biochem J, 432, 485-493.  
19661995 C.D.Sohl, Q.Cheng, and F.P.Guengerich (2009).
Chromatographic assays of drug oxidation by human cytochrome P450 3A4.
  Nat Protoc, 4, 1252-1257.  
19199046 C.R.McCullough, P.K.Pullela, S.C.Im, L.Waskell, and D.S.Sem (2009).
(13)C-Methyl isocyanide as an NMR probe for cytochrome P450 active sites.
  J Biomol NMR, 43, 171-178.  
  19240808 C.Zhou, S.Verma, and B.Blumberg (2009).
The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism.
  Nucl Recept Signal, 7, e001.  
19728720 D.Fishelovitch, S.Shaik, H.J.Wolfson, and R.Nussinov (2009).
Theoretical characterization of substrate access/exit channels in the human cytochrome P450 3A4 enzyme: involvement of phenylalanine residues in the gating mechanism.
  J Phys Chem B, 113, 13018-13025.  
19129847 D.Ghosh, J.Griswold, M.Erman, and W.Pangborn (2009).
Structural basis for androgen specificity and oestrogen synthesis in human aromatase.
  Nature, 457, 219-223.
PDB code: 3eqm
19074530 H.Sun, C.Moore, P.M.Dansette, S.Kumar, J.R.Halpert, and G.S.Yost (2009).
Dehydrogenation of the indoline-containing drug 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (indapamide) by CYP3A4: correlation with in silico predictions.
  Drug Metab Dispos, 37, 672-684.  
19555717 I.G.Denisov, D.J.Frank, and S.G.Sligar (2009).
Cooperative properties of cytochromes P450.
  Pharmacol Ther, 124, 151-167.  
19694439 J.P.Evans, S.Kandel, and P.R.Ortiz de Montellano (2009).
Isocyanides inhibit human heme oxygenases at the verdoheme stage.
  Biochemistry, 48, 8920-8928.  
20046929 L.Tian, and R.A.Friesner (2009).
QM/MM Simulation on P450 BM3 Enzyme Catalysis Mechanism.
  J Chem Theory Comput, 5, 1421-1431.  
20040113 M.Freigassner, H.Pichler, and A.Glieder (2009).
wTuning microbial hosts for membrane protein production.
  Microb Cell Fact, 8, 69.  
19103148 M.K.Pabarcus, N.Hoe, S.Sadeghi, C.Patterson, E.Wiertz, and M.A.Correia (2009).
CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
  Arch Biochem Biophys, 483, 66-74.  
19265398 S.Balaz (2009).
Modeling kinetics of subcellular disposition of chemicals.
  Chem Rev, 109, 1793-1899.  
19397311 S.C.Gay, L.Sun, K.Maekawa, J.R.Halpert, and C.D.Stout (2009).
Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1-biphenyl-4-methyl-1H-imidazole: ligand-induced structural response through alpha-helical repositioning.
  Biochemistry, 48, 4762-4771.
PDB codes: 3g5n 3g93
18395506 A.Nath, C.Fernández, J.N.Lampe, and W.M.Atkins (2008).
Spectral resolution of a second binding site for Nile Red on cytochrome P4503A4.
  Arch Biochem Biophys, 474, 198-204.  
18721112 D.F.Lewis, and Y.Ito (2008).
Human cytochromes P450 in the metabolism of drugs: new molecular models of enzyme-substrate interactions.
  Expert Opin Drug Metab Toxicol, 4, 1181-1186.  
19040328 D.R.Davydov, and J.R.Halpert (2008).
Allosteric P450 mechanisms: multiple binding sites, multiple conformers or both?
  Expert Opin Drug Metab Toxicol, 4, 1523-1535.  
18831537 D.R.Davydov, N.Y.Davydova, and J.R.Halpert (2008).
Allosteric transitions in cytochrome P450eryF explored with pressure-perturbation spectroscopy, lifetime FRET, and a novel fluorescent substrate, Fluorol-7GA.
  Biochemistry, 47, 11348-11359.  
18622598 E.M.Isin, and F.P.Guengerich (2008).
Substrate binding to cytochromes P450.
  Anal Bioanal Chem, 392, 1019-1030.  
18484912 E.Stjernschantz, N.P.Vermeulen, and C.Oostenbrink (2008).
Computational prediction of drug binding and rationalisation of selectivity towards cytochromes P450.
  Expert Opin Drug Metab Toxicol, 4, 513-527.  
18393395 E.Yaffe, D.Fishelovitch, H.J.Wolfson, D.Halperin, and R.Nussinov (2008).
MolAxis: efficient and accurate identification of channels in macromolecules.
  Proteins, 73, 72-86.  
18606741 G.Tai, L.J.Dickmann, N.Matovic, J.J.DeVoss, E.M.Gillam, and A.E.Rettie (2008).
Re-engineering of CYP2C9 to probe acid-base substrate selectivity.
  Drug Metab Dispos, 36, 1992-1997.  
18216722 H.Qiu, S.Taudien, H.Herlyn, J.Schmitz, Y.Zhou, G.Chen, R.Roberto, M.Rocchi, M.Platzer, and L.Wojnowski (2008).
CYP3 phylogenomics: evidence for positive selection of CYP3A4 and CYP3A7.
  Pharmacogenet Genomics, 18, 53-66.  
18026129 J.D.Maréchal, C.A.Kemp, G.C.Roberts, M.J.Paine, C.R.Wolf, and M.J.Sutcliffe (2008).
Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6-drug interactions.
  Br J Pharmacol, 153, S82-S89.  
18976212 K.N.Myasoedova (2008).
New findings in studies of cytochromes P450.
  Biochemistry (Mosc), 73, 965-969.  
18373546 K.Roy, and P.P.Roy (2008).
Exploring QSARs for binding affinity of azoles with CYP2B and CYP3A enzymes using GFA and G/PLS techniques.
  Chem Biol Drug Des, 71, 464-473.  
18622752 K.S.Rabe, V.J.Gandubert, M.Spengler, M.Erkelenz, and C.M.Niemeyer (2008).
Engineering and assaying of cytochrome P450 biocatalysts.
  Anal Bioanal Chem, 392, 1059-1073.  
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
19179758 M.S.Achary, and H.A.Nagarajam (2008).
Comparative docking studies of CYP1b1 and its PCG-associated mutant forms.
  J Biosci, 33, 699-713.  
18096676 P.Kang, M.Liao, M.R.Wester, J.S.Leeder, R.E.Pearce, and M.A.Correia (2008).
CYP3A4-Mediated carbamazepine (CBZ) metabolism: formation of a covalent CBZ-CYP3A4 adduct and alteration of the enzyme kinetic profile.
  Drug Metab Dispos, 36, 490-499.  
18818195 P.R.Porubsky, K.M.Meneely, and E.E.Scott (2008).
Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates.
  J Biol Chem, 283, 33698-33707.
PDB codes: 3e4e 3e6i
17922078 Q.B.Su, F.He, X.D.Wang, S.Guan, Z.Y.Xie, L.Y.Wang, Y.J.Lu, L.Q.Gu, Z.S.Huang, X.Chen, M.Huang, and S.F.Zhou (2008).
Biotransformation and pharmacokinetics of the novel anticancer drug, SYUIQ-5, in the rat.
  Invest New Drugs, 26, 119-137.  
18383336 S.Takahashi, M.Katoh, T.Saitoh, M.Nakajima, and T.Yokoi (2008).
Allosteric kinetics of human carboxylesterase 1: species differences and interindividual variability.
  J Pharm Sci, 97, 5434-5445.  
18004755 W.Li, Y.Tang, H.Liu, J.Cheng, W.Zhu, and H.Jiang (2008).
Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking.
  Proteins, 71, 938-949.  
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.  
  18607105 Z.Chang, L.Li, Z.Pan, and X.Wang (2008).
Crystallization and preliminary X-ray analysis of allene oxide synthase, cytochrome P450 CYP74A2, from Parthenium argentatum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 668-670.  
18431572 Z.Y.Zhang, B.M.King, R.D.Pelletier, and Y.N.Wong (2008).
Delineation of the interactions between the chemotherapeutic agent eribulin mesylate (E7389) and human CYP3A4.
  Cancer Chemother Pharmacol, 62, 707-716.  
17357170 A.Chougnet, Y.Grinkova, D.Ricard, S.Sligar, and W.D.Woggon (2007).
Fluorescent Probes for Rapid Screening of Potential Drug-Drug Interactions at the CYP3A4 Level.
  ChemMedChem, 2, 717-724.  
17459328 A.G.Roberts, and W.M.Atkins (2007).
Energetics of heterotropic cooperativity between alpha-naphthoflavone and testosterone binding to CYP3A4.
  Arch Biochem Biophys, 463, 89.  
17207766 A.J.Annalora, E.Bobrovnikov-Marjon, R.Serda, A.Pastuszyn, S.E.Graham, C.B.Marcus, and J.L.Omdahl (2007).
Hybrid homology modeling and mutational analysis of cytochrome P450C24A1 (CYP24A1) of the Vitamin D pathway: insights into substrate specificity and membrane bound structure-function.
  Arch Biochem Biophys, 460, 262-273.  
17387527 A.R.Shaikh, E.Broclawik, H.Tsuboi, M.Koyama, A.Endou, H.Takaba, M.Kubo, C.A.Del Carpio, and A.Miyamoto (2007).
Oxidation mechanism in the metabolism of (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide on oxyferryl active site in CYP3A4 Cytochrome: DFT modeling.
  J Mol Model, 13, 851-860.  
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.  
17985934 A.Z.Kijac, Y.Li, S.G.Sligar, and C.M.Rienstra (2007).
Magic-angle spinning solid-state NMR spectroscopy of nanodisc-embedded human CYP3A4.
  Biochemistry, 46, 13696-13703.  
18020326 D.Fishelovitch, C.Hazan, H.Hirao, H.J.Wolfson, R.Nussinov, and S.Shaik (2007).
QM/MM study of the active species of the human cytochrome P450 3A4, and the influence thereof of the multiple substrate binding.
  J Phys Chem B, 111, 13822-13832.  
17936929 F.P.Guengerich (2007).
Mechanisms of cytochrome P450 substrate oxidation: MiniReview.
  J Biochem Mol Toxicol, 21, 163-168.  
17253156 G.Caron, G.Ermondi, and B.Testa (2007).
Predicting the oxidative metabolism of statins: an application of the MetaSite algorithm.
  Pharm Res, 24, 480-501.  
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.  
17274942 H.Fernando, D.R.Davydov, C.C.Chin, and J.R.Halpert (2007).
Role of subunit interactions in P450 oligomers in the loss of homotropic cooperativity in the cytochrome P450 3A4 mutant L211F/D214E/F304W.
  Arch Biochem Biophys, 460, 129-140.  
17279501 H.Yuki, Y.Tanaka, M.Hata, H.Ishikawa, S.Neya, and T.Hoshino (2007).
Implementation of pi-pi interactions in molecular dynamics simulation.
  J Comput Chem, 28, 1091-1099.  
17273868 L.Li, H.Cheng, J.Gai, and D.Yu (2007).
Genome-wide identification and characterization of putative cytochrome P450 genes in the model legume Medicago truncatula.
  Planta, 226, 109-123.  
18034311 M.P.Gleeson, A.M.Davis, K.K.Chohan, S.W.Paine, S.Boyer, C.L.Gavaghan, C.H.Arnby, C.Kankkonen, and N.Albertson (2007).
Generation of in-silico cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A4 inhibition QSAR models.
  J Comput Aided Mol Des, 21, 559-573.  
17898899 P.H.Buist (2007).
Exotic biomodification of fatty acids.
  Nat Prod Rep, 24, 1110-1127.  
17705402 P.Lafite, F.André, D.C.Zeldin, P.M.Dansette, and D.Mansuy (2007).
Unusual regioselectivity and active site topology of human cytochrome P450 2J2.
  Biochemistry, 46, 10237-10247.  
17470359 P.Lafite, S.Dijols, D.C.Zeldin, P.M.Dansette, and D.Mansuy (2007).
Selective, competitive and mechanism-based inhibitors of human cytochrome P450 2J2.
  Arch Biochem Biophys, 464, 155-168.  
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.  
17540336 S.Sansen, M.H.Hsu, C.D.Stout, and E.F.Johnson (2007).
Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants.
  Arch Biochem Biophys, 464, 197-206.
PDB codes: 2pg5 2pg6 2pg7
17198380 T.N.Tsalkova, N.Y.Davydova, J.R.Halpert, and D.R.Davydov (2007).
Mechanism of interactions of alpha-naphthoflavone with cytochrome P450 3A4 explored with an engineered enzyme bearing a fluorescent probe.
  Biochemistry, 46, 106-119.  
17085710 Y.Hong, M.Xu, J.Guo, Z.Xu, X.Chen, and G.Sun (2007).
Respiration and growth of Shewanella decolorationis S12 with an Azo compound as the sole electron acceptor.
  Appl Environ Microbiol, 73, 64-72.  
17043816 Y.Hong, X.Chen, J.Guo, Z.Xu, M.Xu, and G.Sun (2007).
Effects of electron donors and acceptors on anaerobic reduction of azo dyes by Shewanella decolorationis S12.
  Appl Microbiol Biotechnol, 74, 230-238.  
16959210 B.Wen, J.N.Lampe, A.G.Roberts, W.M.Atkins, A.David Rodrigues, and S.D.Nelson (2006).
Cysteine 98 in CYP3A4 contributes to conformational integrity required for P450 interaction with CYP reductase.
  Arch Biochem Biophys, 454, 42-54.  
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.  
16785429 E.Ono, M.Nakai, Y.Fukui, N.Tomimori, M.Fukuchi-Mizutani, M.Saito, H.Satake, T.Tanaka, M.Katsuta, T.Umezawa, and Y.Tanaka (2006).
Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)-sesamin.
  Proc Natl Acad Sci U S A, 103, 10116-10121.  
16954196 F.P.Guengerich (2006).
A malleable catalyst dominates the metabolism of drugs.
  Proc Natl Acad Sci U S A, 103, 13565-13566.  
16566594 H.Fernando, J.R.Halpert, and D.R.Davydov (2006).
Resolution of multiple substrate binding sites in cytochrome P450 3A4: the stoichiometry of the enzyme-substrate complexes probed by FRET and Job's titration.
  Biochemistry, 45, 4199-4209.  
16551925 J.H.Atkins, and J.S.Johansson (2006).
Technologies to shape the future: proteomics applications in anesthesiology and critical care medicine.
  Anesth Analg, 102, 1207-1216.  
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.  
17047872 J.Zurek, N.Foloppe, J.N.Harvey, and A.J.Mulholland (2006).
Mechanisms of reaction in cytochrome P450: Hydroxylation of camphor in P450cam.
  Org Biomol Chem, 4, 3931-3937.  
16637647 K.P.Ravindranathan, E.Gallicchio, R.A.Friesner, A.E.McDermott, and R.M.Levy (2006).
Conformational equilibrium of cytochrome P450 BM-3 complexed with N-palmitoylglycine: a replica exchange molecular dynamics study.
  J Am Chem Soc, 128, 5786-5791.  
16892339 M.A.Lill, M.Dobler, and A.Vedani (2006).
Prediction of small-molecule binding to cytochrome P450 3A4: flexible docking combined with multidimensional QSAR.
  ChemMedChem, 1, 73-81.  
16954191 M.Ekroos, and T.Sjögren (2006).
Structural basis for ligand promiscuity in cytochrome P450 3A4.
  Proc Natl Acad Sci U S A, 103, 13682-13687.
PDB codes: 2j0c 2j0d 2v0m
16793528 M.J.de Groot (2006).
Designing better drugs: predicting cytochrome P450 metabolism.
  Drug Discov Today, 11, 601-606.  
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.  
16710330 R.Hili, and A.K.Yudin (2006).
Making carbon-nitrogen bonds in biological and chemical synthesis.
  Nat Chem Biol, 2, 284-287.  
16962139 S.Bencharit, C.C.Edwards, C.L.Morton, E.L.Howard-Williams, P.Kuhn, P.M.Potter, and M.R.Redinbo (2006).
Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1.
  J Mol Biol, 363, 201-214.
PDB codes: 2dqy 2dqz 2dr0 2h7c
16863447 T.Herz, K.Wolf, J.Kraus, and B.Kramer (2006).
4SCan/vADME: intelligent library screening as a shortcut from hits to lead compounds.
  Expert Opin Drug Metab Toxicol, 2, 471-484.  
17073518 T.S.Tracy (2006).
Atypical cytochrome p450 kinetics: implications for drug discovery.
  Drugs R D, 7, 349-363.  
16485904 U.M.Kent, H.L.Lin, D.E.Mills, K.A.Regal, and P.F.Hollenberg (2006).
Identification of 17-alpha-ethynylestradiol-modified active site peptides and glutathione conjugates formed during metabolism and inactivation of P450s 2B1 and 2B6.
  Chem Res Toxicol, 19, 279-287.  
16859405 W.M.Atkins (2006).
Current views on the fundamental mechanisms of cytochrome P450 allosterism.
  Expert Opin Drug Metab Toxicol, 2, 573-579.  
15720389 B.Sielaff, and J.R.Andreesen (2005).
Kinetic and binding studies with purified recombinant proteins ferredoxin reductase, ferredoxin and cytochrome P450 comprising the morpholine mono-oxygenase from Mycobacterium sp. strain HE5.
  FEBS J, 272, 1148-1159.  
17193178 B.Testa, A.L.Balmat, A.Long, and P.Judson (2005).
Predicting drug metabolism--an evaluation of the expert system METEOR.
  Chem Biodivers, 2, 872-885.  
16052607 C.Sun, J.R.Huth, and P.J.Hajduk (2005).
NMR in pharmacokinetic and pharmacodynamic profiling.
  Chembiochem, 6, 1592-1600.  
  16041916 C.U.Nnadi, J.F.Goldberg, and A.K.Malhotra (2005).
Genetics and psychopharmacology: prospects for individualized treatment.
  Essent Psychopharmacol, 6, 193-208.  
  16639181 C.U.Nnadi, J.F.Goldberg, and A.K.Malhotra (2005).
Pharmacogenetics in mood disorder.
  Curr Opin Psychiatry, 18, 33-39.  
16004552 D.A.Hesselink, T.van Gelder, and R.H.van Schaik (2005).
The pharmacogenetics of calcineurin inhibitors: one step closer toward individualized immunosuppression?
  Pharmacogenomics, 6, 323-337.  
15834000 D.R.Davydov, A.E.Botchkareva, N.E.Davydova, and J.R.Halpert (2005).
Resolution of two substrate-binding sites in an engineered cytochrome P450eryF bearing a fluorescent probe.
  Biophys J, 89, 418-432.  
15653318 E.E.Scott, and J.R.Halpert (2005).
Structures of cytochrome P450 3A4.
  Trends Biochem Sci, 30, 5-7.  
16243264 G.Zlokarnik, P.D.Grootenhuis, and J.B.Watson (2005).
High throughput P450 inhibition screens in early drug discovery.
  Drug Discov Today, 10, 1443-1450.  
16028060 J.Bojunga, C.Welsch, I.Antes, M.Albrecht, T.Lengauer, and S.Zeuzem (2005).
Structural and functional analysis of a novel mutation of CYP21B in a heterozygote carrier of 21-hydroxylase deficiency.
  Hum Genet, 117, 558-564.  
16059671 J.M.Kriegl, T.Arnhold, B.Beck, and T.Fox (2005).
A support vector machine approach to classify human cytochrome P450 3A4 inhibitors.
  J Comput Aided Mol Des, 19, 189-201.  
15993809 M.Congreve, C.W.Murray, and T.L.Blundell (2005).
Structural biology and drug discovery.
  Drug Discov Today, 10, 895-907.  
16272806 M.Hashida (2005).
[In-silico prediction of pharmacokinetic properties]
  Yakugaku Zasshi, 125, 853-861.  
16922645 S.Ekins, S.Andreyev, A.Ryabov, E.Kirillov, E.A.Rakhmatulin, A.Bugrim, and T.Nikolskaya (2005).
Computational prediction of human drug metabolism.
  Expert Opin Drug Metab Toxicol, 1, 303-324.  
15803155 S.Neidle, and D.E.Thurston (2005).
Chemical approaches to the discovery and development of cancer therapies.
  Nat Rev Cancer, 5, 285-296.  
16204965 S.Tsukamoto, M.Aburatani, T.Yoshida, Y.Yamashita, A.A.El-Beih, and T.Ohta (2005).
CYP3A4 inhibitors isolated from Licorice.
  Biol Pharm Bull, 28, 2000-2002.  
16272754 T.Funahashi, Y.Tanaka, S.Yamaori, T.Kimura, T.Matsunaga, S.Ohmori, T.Kageyama, I.Yamamoto, and K.Watanabe (2005).
Stimulatory effects of testosterone and progesterone on the NADH- and NADPH-dependent oxidation of 7beta-hydroxy-delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol in monkey liver microsomes.
  Drug Metab Pharmacokinet, 20, 358-367.  
15832445 W.M.Atkins (2005).
Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions.
  Annu Rev Pharmacol Toxicol, 45, 291-310.  
  15663291 K.Fujita (2004).
Food-drug interactions via human cytochrome P450 3A (CYP3A).
  Drug Metabol Drug Interact, 20, 195-217.  
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.