このページはRCSBの David S. Goodsell博士による「Molecule of the Month」2006年10月の記事を日本語に訳したものです。転載・引用については利用規約をご覧下さい。
「今月の分子」一覧に戻る / この記事のRCSBオリジナルサイト(英語)を見る
:翻訳 工藤高裕 (PDBj)
シトクロムp450の一種CYP3A4とそれに含まれるヘム(赤)(上:PDB:1w0e、下:PDB:2j0d、抗生物質のエリスロマイシン(青)も結合している)

頭痛がして痛み止めの薬を飲むと、薬の効果は数時間もすると薄れていくのに気づくだろう。これは、体内に強力な解毒機構があって、薬のような異物を見つけると身体から排出してしまうために起こる現象である。この解毒機構は私たちが食べたり呼吸したりして取り込まれたあらゆる種類の不快な化学物質〜薬、植物の有毒物質、調理でできた発がん物質、環境汚染物質など〜と戦っている。シトクロムp450酵素は、この化学的な戦いにおける最初の防衛線となる酵素である。

酸素の付加

シトクロムp450酵素は見慣れない分子を見つけ出して酸素を付加する。多くの場合、この作用によって分子はより水に溶けやすくなり、身体から排出しやすくなる。毒性分子に付加された酸素は、他の解毒酵素がすぐに使えるハンドルとなり、これを土台にして更に修正が行われ、破壊される。この酸素を付加する仕事は化学的に扱いにくく、シトクロムp450酵素はこの反応を行うのに強力な分子の道具〜ヘム基(heme group)の鉄原子〜を使う(詳細は後述)。

どこにでもある p450

シトクロムp450酵素はあらゆる生物で見られる。各生物は何種類かの酵素を作り、それぞれが異なる分子を選んで作用する。通常、細菌は約20種類の、我々は約60種類のシトクロムp450酵素を作る。植物は何百種類ものシトクロムp450酵素を作っていることが多い。これは植物が自分自身を守るために独特の色素と変わった毒素を作るからである。反応の多くはこれらの分子を作るのに必要で、特化したシトクロムp450酵素によって行われる。なお、遺伝的視点から見たシトクロムp450に関する追加情報を欧州バイオインフォマティクス研究所(EBI)の「 今月のタンパク質 」で見ることができる。

両刃の剣

ここに示した分子はCYP3A4(PDBエントリー 1w0e 、PDBエントリー 2j0d )で、体内の薬剤無毒化において重要な役割を果たすシトクロムp450である。この酵素は既知の薬の約半数に作用すると考えられている。例えば、この分子は抗生物質のエリスロマイシン(右図下の青い分子)に修飾を加える。また、コデイン(codeine、麻薬性鎮咳薬)、ジアゼパム(diazepam、米国での商品名はバリウム Valium、日本での商品名はセルシン、ホリゾン、抗不安薬)、パクリタキセル(paclitaxel、商品名タキソール Taxol、抗がん剤)、および抗エイズ薬(anti-HIV drug)などさまざまな薬に対しても無毒化作用を行う。

ところが場合によって、シトクロムp450によって行われる反応は有用というよりむしろ有害となりうる。例えば、CYP3A4はアセトアミノフェン(アセトアミノフェン、商品名タイレノール Tylenol、解熱鎮痛薬)を過剰に摂取した時の毒性に関する部分的原因となっている。改変されたアセトアミノフェンは危険なぐらい反応性が高いが、通常は他の解毒酵素によって速やかに排出される。しかし過剰に摂取すると、反応性の高い中間体が危険な水準にまで増えてしまう。

処方箋とp450

医師は投薬指示を行う際、シトクロムp450酵素のことを忘れないよう注意しなければならない。例えば、処方箋にこのような警告を見るかもしれない。「薬を飲む時、グレープフルーツジュースで飲まないでください。」グレープフルーツにはシトクロムp450酵素の働きを阻害するフラビノール(flavinol)分子を含んでいる。フラビノールが薬剤の解毒化を遅らせ、医師の予想よりも薬の効果が強まることになるかもしれない。

合成の魔法使い

左:ステロール合成を行う結核菌のシトクロムp450(PDB:1ea1) 右:コレステロールの合成を行うシトクロムp450(PDB:1e6e)

シトクロムp450酵素は、通常の細胞構成物の合成でも欠かすことのできない様々な役割を果たしている。例えば、特別なシトクロムp450酵素が、信号伝達に関わるステロイド、ビタミンAとD、脂肪様のエイコサノイドといった分子を構築する化学反応段階を行うよう作られている。図の左に示した酵素は菌類のシトクロムp450(PDBエントリー 1ea1 )でステロール合成の一段階を行う。我々の細胞にあるこれに似た酵素がコレステロールの合成に必要である。図の右に示した酵素複合体(PDBエントリー 1e6e )はこの反応に必要な電子を提供する。

構造を見る

樟脳に酸素を付加するシトクロムp450cam(左:反応前、PDB:3cpp 右:反応後、PDB:1noo)

最もよく研究されているシトクロムp450酵素は細菌の酵素で、樟脳(camphor)に酸素を付加するものである。ここに示した2例の酵素は、シトクロムp450camと呼ばれる。左に示したのは、樟脳と一酸化炭素が活性部位に結合したPDBエントリー 3cpp の構造である。一酸化炭素はこの酵素にとって有毒な阻害剤である。一酸化炭素は酸素ガスと同じ場所で鉄(ヘムの中央にある大きな黄色い球)と結合する。鉄の下にあるシステインアミノ酸が鉄を活性化する。右に示したのはPDBエントリー 1noo の構造で、反応後の樟脳を示している。樟脳に酸素分子が付加されて、他の酸素原子が水分子から取り除かれている。PDBを見ると、シトクロムp450camの構造が何十個も見つけることができる。小さな活性部位にさまざまな分子が結合し、反応の様々な段階が示されているのが分かる。

2006/10/01 にキーワード検索を行って得られた「cytochrome p450」関連PDBエントリー一覧はこちらのリスト

2006/10/01 キーワード検索による関連PDBエントリー一覧
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PDB ID Title Authors Publication Year Journal Name Volume No First Page Pubmed ID
1akd Crystal structure of cytochrome P-450cam complexed with the (1S)-camphor enantiomer. Schlichting, I., Jung, C., Schulze, H. 1997 FEBS Lett. 415 253 9357977
1amo Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Wang, M., Roberts, D.L., Paschke, R., Shea, T.M., Masters, B.S., Kim, J.J. 1997 Proc.Natl.Acad.Sci.USA 94 8411 9237990
1b1c Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution. Zhao, Q., Modi, S., Smith, G., Paine, M., McDonagh, P.D., Wolf, C.R., Tew, D., Lian, L.Y., Roberts, G.C., Driessen, H.P. 1999 Protein Sci. 8 298 10048323
1bu7 Structure of a cytochrome P450-redox partner electron-transfer complex. Sevrioukova, I.F., Li, H., Zhang, H., Peterson, J.A., Poulos, T.L. 1999 Proc.Natl.Acad.Sci.USA 96 1863 10051560
1bvy
1cl6 Proton delivery in NO reduction by fungal nitric-oxide reductase. Cryogenic crystallography, spectroscopy, and kinetics of ferric-NO complexes of wild-type and mutant enzymes. Shimizu, H., Obayashi, E., Gomi, Y., Arakawa, H., Park, S.Y., Nakamura, H., Adachi, S., Shoun, H., Shiro, Y. 2000 J.Biol.Chem. 275 4816 10671516
1cmj
1cmn
1cp4 Formation, crystal structure, and rearrangement of a cytochrome P-450cam iron-phenyl complex. Raag, R., Swanson, B.A., Poulos, T.L., Ortiz de Montellano, P.R. 1990 Biochemistry 29 8119 2261467
1cpo The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid. Sundaramoorthy, M., Terner, J., Poulos, T.L. 1995 Structure 3 1367 8747463
2cpo
1cpt Crystal structure and refinement of cytochrome P450terp at 2.3 A resolution. Hasemann, C.A., Ravichandran, K.G., Peterson, J.A., Deisenhofer, J. 1994 J.Mol.Biol. 236 1169 8120894
1ddg Four crystal structures of the 60 kDa flavoprotein monomer of the sulfite reductase indicate a disordered flavodoxin-like module. Gruez, A., Pignol, D., Zeghouf, M., Coves, J., Fontecave, M., Ferrer, J.L., Fontecilla-Camps, J.C. 2000 J.Mol.Biol. 299 199 10860732
1ddi
1dt6 Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity. Williams, P.A., Cosme, J., Sridhar, V., Johnson, E.F., McRee, D.E. 2000 Mol.Cell 5 121 10678174
1dz4 The catalytic pathway of cytochrome p450cam at atomic resolution. Schlichting, I., Berendzen, J., Chu, K., Stock, A.M., Maves, S.A., Benson, D.E., Sweet, R.M., Ringe, D., Petsko, G.A., Sligar, S.G. 2000 Science 287 1615 10698731
1dz6
1dz8
1dz9
1e6e Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis. Muller, J.J., Lapko, A., Bourenkov, G., Ruckpaul, K., Heinemann, U. 2001 J.Biol.Chem. 276 2786 11053423
1e9x Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors Podust, L.M., Poulos, T.L., Waterman, M.R. 2001 Proc.Natl.Acad.Sci.USA 98 3068 11248033
1ea1
1egy Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity. Cupp-Vickery, J., Anderson, R., Hatziris, Z. 2000 Proc.Natl.Acad.Sci.USA 97 3050 10716705
1eup
1ehe Crystal structures of cytochrome P450nor and its mutants (Ser286-->Val, Thr) in the ferric resting state at cryogenic temperature: a comparative analysis with monooxygenase cytochrome P450s. Shimizu, H., Park, S., Lee, D., Shoun, H., Shiro, Y. 2000 J.Inorg.Biochem. 81 191 11051564
1ehf
1ehg
1f20 Crystal structure of the FAD/NADPH-binding domain of rat neuronal nitric-oxide synthase. Comparisons with NADPH-cytochrome P450 oxidoreductase. Zhang, J., Martasek, P., Paschke, R., Shea, T., Siler Masters, B.S., Kim, J.J. 2001 J.Biol.Chem. 276 37506 11473123
1f24 Mutation effects of a conserved threonine (Thr243) of cytochrome P450nor on its structure and function. Shimizu, H., PARK, S.-Y. 2000 J.Inorg.Biochem. 82 103 11132616
1f25
1f26
1f4t Crystal structure of a thermophilic cytochrome P450 from the archaeon Sulfolobus solfataricus. Yano, J.K., Koo, L.S., Schuller, D.J., Li, H., Ortiz de Montellano, P.R., Poulos, T.L. 2000 J.Biol.Chem. 275 31086 10859321
1f4u
1fag The structure of the cytochrome p450BM-3 haem domain complexed with the fatty acid substrate, palmitoleic acid. Li, H., Poulos, T.L. 1997 Nat.Struct.Biol. 4 140 9033595
1fah The role of Thr268 in oxygen activation of cytochrome P450BM-3. Yeom, H., Sligar, S.G., Li, H., Poulos, T.L., Fulco, A.J. 1995 Biochemistry 34 14733 7578081
1ged A positively charged cluster formed in the heme-distal pocket of cytochrome P450nor is essential for interaction with NADH Kudo, T., Takaya, N., Park, S.-Y., Shiro, Y., Shoun, H. 2001 J.Biol.Chem. 276 5020 11076941
1gei Structural characterization of n-butyl-isocyanide complexes of cytochromes P450nor and P450cam. Lee, D.S., Park, S.Y., Yamane, K., Obayashi, E., Hori, H., Shiro, Y. 2001 Biochemistry 40 2669 11258878
1gej
1gek
1gem
1gjm Covalent Attachment of an Electroactive Sulphydryl Reagent in the Active Site of Cytochrome P450Cam as Revealed by the Crystal Structure of the Modified Protein Digleria, K., Nickerson, D.P., Hill, H.A.O., Wong, L.-L., Fulop, V. 1998 J.Am.Chem.Soc. 120 46 n/a
1gwi The 1.92-A structure of Streptomyces coelicolor A3(2) CYP154C1. A new monooxygenase that functionalizes macrolide ring systems. Podust, L., Kim, Y., Arase, M., Neely, B., Beck, B., Bach, H., Sherman, D., Lamb, D., Kelly, S., Waterman, M. 2003 J.Biol.Chem. 278 12214 12519772
1h5z Estriol bound and ligand-free structures of sterol 14alpha-demethylase. Podust, L.M., Yermalitskaya, L.V., Lepesheva, G.I., Dalmasso, V.N.Podu E.A., Waterman, M.R. 2004 Structure 12 1937 15530358
1io7 Crystallization and preliminary X-ray diffraction analysis of a cytochrome P450 (CYP119) from Sulfolobus solfataricus. Park, S.Y., Yamane, K., Adachi, S., Shiro, Y., Weiss, K.E., Sligar, S.G. 2000 Acta Crystallogr., Sect.D 56 1173 10957637
1io8
1io9
1izo Substrate Recognition and Molecular Mechanism of Fatty Acid Hydroxylation by Cytochrome P450 from Bacillus subtilis. CRYSTALLOGRAPHIC, SPECTROSCOPIC, AND MUTATIONAL STUDIES. Lee, D.S., Yamada, A., Sugimoto, H., Matsunaga, I., Ogura, H., Ichihara, K., Adachi, S., Park, S.Y., Shiro, Y. 2003 J.Biol.Chem. 278 9761 12519760
1j9z NADPH-cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer. Hubbard, P.A., Shen, A.L., Paschke, R., Kasper, C.B., Kim, J.J. 2001 J.Biol.Chem. 276 29163 11371558
1ja0
1ja1
1jfb X-ray structure of nitric oxide reductase (cytochrome P450nor) at atomic resolution Shimizu, H., Park, S.Y., Shiro, Y., Adachi, S. 2002 Acta Crystallogr., Sect.D 58 81 11752781
1jfc
1jin Ketoconazole-induced conformational changes in the active site of cytochrome P450eryF. Cupp-Vickery, J.R., Garcia, C., Hofacre, A., McGee-Estrada, K. 2001 J.Mol.Biol. 311 101 11469860
1jio
1jip
1jme Structural and spectroscopic analysis of the F393H mutant of flavocytochrome P450 BM3. Ost, T.W., Munro, A.W., Mowat, C.G., Taylor, P.R., Pesseguiero, A., Fulco, A.J., Cho, A.K., Cheesman, M.A., Walkinshaw, M.D., Chapman, S.K. 2001 Biochemistry 40 13430 11695889
1jpz Pivotal role of water in the mechanism of P450BM-3. Haines, D.C., Tomchick, D.R., Machius, M., Peterson, J.A. 2001 Biochemistry 40 13456 11695892
1k2o Probing the open state of cytochrome P450cam with ruthenium-linker substrates. Dunn, A.R., Dmochowski, I.J., Bilwes, A.M., Gray, H.B., Crane, B.R. 2001 Proc.Natl.Acad.Sci.USA 98 12420 11606730
1lfk Crystal Structure of OxyB, a Cytochrome P450 Implicated in an Oxidative Phenol Coupling Reaction during Vancomycin Biosynthesis. Zerbe, K., Pylypenko, O., Vitali, F., Zhang, W., Rouset, S., Heck, M., Vrijbloed, J.W., Bischoff, D., Bister, B., Sussmuth, R.D., Pelzer, S., Wohlleben, W., Robinson, J.A., Schlichting, I. 2002 J.Biol.Chem. 277 47476 12207020
1lg9
1lgf
1lwl Fluorescent probes for cytochrome P450 structural characterization and inhibitor screening Dunn, A.R., Hays, A.M., Goodin, D.B., Stout, C.D., Chiu, R., Winkler, J.R., Gray, H.B. 2002 J.AM.CHEM.SOC. 124 10254 12197708
1n40 Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450. Leys, D., Mowat, C.G., McLean, K.J., Richmond, A., Chapman, S.K., Walkinshaw, M.D., Munro, A.W. 2003 J.Biol.Chem. 278 5141 12435731
1n4g
1n6b Structure of a Substrate Complex of Mammalian Cytochrome P450 2C5 at 2.3 A Resolution: Evidence for Multiple Substrate Binding Modes Wester, M.R., Johnson, E.F., Marques-Soares, C., Dansette, P.M., Mansuy, D., Stout, C.D. 2003 Biochemistry 42 6370 12767218
1n97 Preliminary Characterization and Crystal Structure of a Thermostable Cytochrome P450 from Thermus thermophilus Yano, J.K., Blasco, F., Li, H., Schmid, R.D., Henne, A., Poulos, T.L. 2003 J.Biol.Chem. 278 608 12401810
1nr6 Structure of Mammalian Cytochrome P450 2C5 Complexed with Diclofenac at 2.1 A Resolution: Evidence for an Induced Fit Model of Substrate Binding WESTER, M.R., JOHNSON, E.F., Marques-Soares, C., Dijols, S., Dansette, P.M., Mansuy, D., STOUT, C.D. 2003 Biochemistry 42 9335 12899620
1o76 rystal structures of cyanide complexes of P450cam and the oxygenase domain of inducible nitric oxide synthase-structural models of the short-lived oxygen complexes. Fedorov, R., Ghosh, D., Schlichting, I. 2003 Arch.Biochem.Biophys. 409 25 12464241
1odo Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways. Podust, L.M., Bach, H., Kim, Y., Lamb, D.C., Arase, M., Kelly, D.H.Sherma S.L., Waterman, M.R. 2004 Protein Sci. 13 255 14691240
1og2 Crystal structure of human cytochrome P450 2C9 with bound warfarin. Williams, P.A., Cosme, J., Ward, A., Angove, H.C., Matak Vinkovic, D., Jhoti, H. 2003 Nature 424 464 12861225
1og5
1oxa Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Cupp-Vickery, J.R., Poulos, T.L. 1995 Nat.Struct.Biol. 2 144 7749919
1p0v Oxygen Activation and Electron Transfer in Flavocytochrome P450 BM3 Ost, T.W.B., Clark, J., Mowat, C.G., Miles, C.S., Walkinshaw, M.D., Reid, G.A., Chapman, S.K., Daff, S. 2003 J.Am.Chem.Soc. 125 15010 14653735
1p0w
1p0x
1pha Inhibitor-induced conformational change in cytochrome P-450CAM. Raag, R., Li, H., Jones, B.C., Poulos, T.L. 1993 Biochemistry 32 4571 8485133
1phb
1phc Crystal structure of substrate-free Pseudomonas putida cytochrome P-450. Poulos, T.L., Finzel, B.C., Howard, A.J. 1986 Biochemistry 25 5314 3768350
1phd Crystal structures of metyrapone- and phenylimidazole-inhibited complexes of cytochrome P-450cam. Poulos, T.L., Howard, A.J. 1987 Biochemistry 26 8165 3442650
1phe
1phf
1phg
1po5 An open conformation of mammalian cytochrome P450 2B4 at 1.6 A resolution Scott, E.E., He, Y.A., Wester, M.R., White, M.A., Chin, C.C., Halpert, J.R., Johnson, E.F., Stout, C.D. 2003 Proc.Natl.Acad.Sci.USA 100 13196 14563924
1pq2 Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site Schoch, G.A., Yano, J.K., Wester, M.R., Griffin, K.J., Stout, C.D., Johnson, E.F. 2004 J.Biol.Chem. 279 9497 14676196
1q5d Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK Nagano, S., Li, H., Shimizu, H., Nishida, C., Ogura, H., Ortiz de Montellano, P.R., Poulos, T.L. 2003 J.Biol.Chem. 278 44886 12933799
1q5e
1qmq Optical detection of cytochrome P450 by sensitizer-linked substrates. Dmochowski, I.J., Crane, B.R., Wilker, J.J., Winkler, J.R., Gray, H.B. 1999 Proc.Natl.Acad.Sci.USA 96 12987 10557259
1r9o The Structure of Human Cytochrome P450 2C9 Complexed with Flurbiprofen at 2.0 A Resolution Wester, M.R., Yano, J.K., Schoch, G.A., Yang, C., Griffin, K.J., Stout, C.D., Johnson, E.F. 2004 J.Biol.Chem. 279 35630 15181000
1rom Crystal structure of nitric oxide reductase from denitrifying fungus Fusarium oxysporum. Park, S.Y., Shimizu, H., Adachi, S., Nakagawa, A., Tanaka, I., Nakahara, K., Shoun, H., Obayashi, E., Nakamura, H., Iizuka, T., Shiro, Y. 1997 Nat.Struct.Biol. 4 827 9334748
2rom
1s1f Binding of Two Flaviolin Substrate Molecules, Oxidative Coupling, and Crystal Structure of Streptomyces coelicolor A3(2) Cytochrome P450 158A2 Zhao, B., Guengerich, F.P., Bellamine, A., Lamb, D.C., Izumikawa, M., Lei, L., Podust, L.M., Sundaramoorthy, M., Kalaitzis, J.A., Reddy, L.M., Kelly, S.L., Moore, B.S., Stec, D., Voehler, M., Falck, J.R., Shimada, T., Waterman, M.R. 2005 J.Biol.Chem. 280 11599 15659395
1se6 Binding of Two Flaviolin Substrate Molecules, Oxidative Coupling, and Crystal Structure of Streptomyces coelicolor A3(2) Cytochrome P450 158A2. Zhao, B., Guengerich, F.P., Bellamine, A., Lamb, D.C., Izumikawa, M., Lei, L., Podust, L.M., Sundaramoorthy, M., Kalaitzis, J.A., Reddy, L.M., Kelly, S.L., Moore, B.S., Stec, D., Voehler, M., Falck, J.R., Shimada, T., Waterman, M.R. 2005 J.Biol.Chem. 280 11599 15659395
1t93
1smi A Single Mutation in Cytochrome P450 BM3 Induces the Conformational Rearrangement Seen upon Substrate Binding in the Wild-type Enzyme Joyce, M.G., Girvan, H.M., Munro, A.W., Leys, D. 2004 J.Biol.Chem. 279 23287 15020590
1smj
1suo Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9 angstrom resolution: Insight into the range of P450 conformations and coordination of redox partner binding. Scott, E.E., White, M.A., He, Y.A., Johnson, E.F., Stout, C.D., Halpert, J.R. 2004 J.Biol.Chem. 279 27294 15100217
1t85 Crystal structure of the cytochrome p450cam mutant that exhibits the same spectral perturbations induced by putidaredoxin binding Nagano, S., Tosha, T., Ishimori, K., Morishima, I., Poulos, T.L. 2004 J.Biol.Chem. 279 42844 15269210
1t86
1t87
1t88
1tqn The Structure of Human Microsomal Cytochrome P450 3A4 Determined by X-ray Crystallography to 2.05-A Resolution Yano, J.K., Wester, M.R., Schoch, G.A., Griffin, K.J., Stout, C.D., Johnson, E.F. 2004 J.Biol.Chem. 279 38091 15258162
1u13 Crystal structure analysis of the C37L/C151T/C442A-triple mutant of CYP51 from Mycobacterium tuberculosis Podust, L.M., Yermalitskaya, L.V., Kim, Y., Waterman, M.R. n/a To be published n/a n/a n/a
1ue8 Structure and direct electrochemistry of cytochrome P450 from the thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain 7 Oku, Y., Ohtaki, A., Kamitori, S., Nakamura, N., Yohda, M., Ohno, H., Kawarabayasi, Y. 2004 J.Inorg.Biochem. 98 1194 15219985
1ued Crystal structure of OxyC, a cytochrome P450 implicated in an oxidative C-C coupling reaction during vancomycin biosynthesis Pylypenko, O., Vitali, F., Zerbe, K., Robinson, J.A., Schlichting, I. 2003 J.Biol.Chem. 278 46727 12888556
1ulw Structural evidence for direct hydride transfer from NADH to cytochrome P450nor Oshima, R., Fushinobu, S., Su, F., Zhang, L., Takaya, N., Shoun, H. 2004 J.Mol.Biol. 342 207 15313618
1xqd
1uyu A Survey of Active Site Access Channels in Cytochromes P450 Wade, R.C., Winn, P.J., Schlichting, I., Sudarko 2004 J.Inorg.Biochem. 98 1175 n/a
1w0e Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone Williams, P.A., Cosme, J., Vinkovic, D.M., Ward, A., Angove, H.C., Day, P.J., Vonrhein, C., Tickle, I.J., Jhoti, H. 2004 Science 305 683 n/a
1w0f
1w0g
1wiy Crystal Structure Analysis of Cytochrome P450 from Thermus thermophilus HB8 Kousumi, Y., Nakagawa, N., Kaneko, M., Yamamoto, H., Masui, R., Kuramitsu, S., Ueyama, N. n/a To be Published n/a n/a n/a
1x8v Estriol Bound and Ligand-free Structures of Sterol 14alpha-Demethylase. Podust, L.M., Yermalitskaya, L.V., Lepesheva, G.I., Podust, V.N., Dalmasso, E.A., Waterman, M.R. 2004 Structure 12 1937 15530358
1yqo The role of Thr268 and Phe393 in cytochrome P450 BM3. Clark, J.P., Miles, C.S., Mowat, C.G., Walkinshaw, M.D., Reid, G.A., Daff, S.N., Chapman, S.K. 2006 J.Inorg.Biochem. 100 1075 16403573
1yqp
1z10 Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen Yano, J.K., Hsu, M.H., Griffin, K.J., Stout, C.D., Johnson, E.F. 2005 Nat.Struct.Mol.Biol. 12 822 16086027
1z11
1z8o Crystal Structures of the Ferrous Dioxygen Complex of Wild-Type Cytochrome P450Eryf and its Mutants, A245S and A245T: Investigation of the Proton Transfer System in P450Eryf Nagano, S., Cupp-Vickery, J.R., Poulos, T.L. 2005 J.Biol.Chem. 280 22102 15824115
1z8p
1z8q
1zo4 Active Site Mutations of P450BM-3 that Dramatically Affect Substrate Binding and Product Formation Hegda, A., Chen, B., Haines, D.C., Bondlela, M., Mullin, D., Graham, S.E., Tomchick, D.R., Machius, M., Peterson, J.A. n/a To be Published n/a n/a n/a
1zoa
1zo9 Interactions of Substrates at the Surface of P450s: A Novel Design for P450 Inhibitors Hegda, A., Chen, B., Tomchick, D.R., Bondlela, M., Haines, D.C., Schaffer, N., Machius, M., Graham, S.E., Peterson, J.A. n/a To be Published n/a n/a n/a
2a1m Crystallographic study on the dioxygen complex of wild-type and mutant cytochrome P450cam. Implications for the dioxygen activation mechanism Nagano, S., Poulos, T.L. 2005 J.Biol.Chem. 280 31659 15994329
2a1n
2a1o
2bdm Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction. Zhao, Y., White, M.A., Muralidhara, B.K., Sun, L., Halpert, J.R., Stout, C.D. 2006 J.Biol.Chem. 281 5973 16373351
2bf4 A Second Fmn-Binding Site in Yeast Nadph-Cytochrome P450 Reductase Suggests a Mechanism of Electron Transfer by Diflavin Reductases. Lamb, D.C., Kim, Y., Yermalitskaya, L.V., Yermalitsky, V.N., Lepesheva, G.I., Kelly, S.L., Waterman, M.R., Podust, L.M. 2006 Structure 14 51 16407065
2bn4
2bmh Modeling Protein-Substrate Interactions in the Heme Domain of Cytochrome P450Bm-3 Li, H., Poulos, T.L. 1995 Acta Crystallogr.,Sect.D 51 21 15299332
2bpo Crystal Structure of the Yeast Cpr Triple Mutant: D74G, Y75F, K78A. Yermalitskaya, L.V., Kim, Y., Waterman, M.R., Podust, L.M. n/a To be Published n/a n/a n/a
2bt6 Light-Induced Reduction of Bovine Adrenodoxin Via the Covalently Bound Ruthenium(II) Bipyridyl Complex: Intramolecular Electron Transfer and Crystal Structure. Halavaty, A., Mueller, J.J., Contzen, J., Jung, C., Hannemann, F., Bernhardt, R., Galander, M., Lendzian, F., Heinemann, U. 2006 Biochemistry 45 709 16411746
2bvj The Structural Basis for Substrate Anchoring, Active Site Selectivity, and Product Formation by P450 Pikc from Streptomyces Venezuelae. Sherman, D.H., Li, S., Yermalitskaya, L.V., Kim, Y., Smith, J.A., Waterman, M.R., Podust, L.M. 2006 J.Biol.Chem. 281 26289 16825192
2c6h
2c7x
2cii
2cp4 Crystal structure of the cytochrome P-450CAM active site mutant Thr252Ala. Raag, R., Martinis, S.A., Sligar, S.G., Poulos, T.L. 1991 Biochemistry 30 11420 1742281
3cp4
4cp4
2cpp High-resolution crystal structure of cytochrome P450cam. Poulos, T.L., Finzel, B.C., Howard, A.J. 1987 J.Mol.Biol. 195 687 3656428
2d09 Role of active site water molecules and substrate hydroxyl groups in oxygen activation by cytochrome P450 158A2: a new mechanism of proton transfer Zhao, B., Guengerich, F.P., Voehler, M., Waterman, M.R. 2005 J.Biol.Chem. 280 42188 16239228
2d0e
2evk Structures of thiolate- and carboxylate-ligated ferric H93G myoglobin: models for cytochrome P450 and for oxyanion-bound heme proteins. Qin, J., Perera, R., Lovelace, L.L., Dawson, J.H., Lebioda, L. 2006 Biochemistry 45 3170 16519512
2evp Structures of Thiolate- and Carboxylate-Ligated Ferric H93G Myoglobin: Models for Cytochrome P450 and for Oxyanion-Bound Heme Proteins(,). Qin, J., Perera, R., Lovelace, L.L., Dawson, J.H., Lebioda, L. 2006 Biochemistry 45 3170 16519512
2f9q Crystal Structure of Human Cytochrome P450 2D6 Rowland, P., Blaney, F.E., Smyth, M.G., Jones, J.J., Leydon, V.R., Oxbrow, A.K., Lewis, C.J., Tennant, M.G., Modi, S., Eggleston, D.S., Chenery, R.J., Bridges, A.M. 2006 J.Biol.Chem. 281 7614 16352597
2fe6 The status of high-valent metal oxo complexes in the P450 cytochromes. Makris, T.M., Koenig, K., Schlichting, I., Sligar, S.G. 2006 J.Inorg.Biochem. 100 507 16510191
2fer
2feu
2h6p Alloreactivity between disparate cognate and allogeneic pMHC-I complexes is resultant of highly focused, peptide-dependent structural mimicry Archbold, J.K., Macdonald, W.A., Miles, J.J., Brennan, R.M., Kjer-Nielsen, L., McCluskey, J., Burrows, S.R., Rossjohn, J. 2006 J.Biol.Chem. 281 34324 16963442
2hpd Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Ravichandran, K.G., Boddupalli, S.S., Hasermann, C.A., Peterson, J.A., Deisenhofer, J. 1993 Science 261 731 8342039
2j0c Structural Basis for Ligand Promiscuity in Cytochrome P450 3A4 Ekroos, M., Sjogren, T. 2006 Proc.Natl.Acad.Sci.USA 103 13682 16954191
2j0d
32c2 Structure of an activity suppressing Fab fragment to cytochrome P450 aromatase: insights into the antibody-antigen interactions. Sawicki, M.W., Ng, P.C., Burkhart, B.M., Pletnev, V.Z., Higashiyama, T., Osawa, Y., Ghosh, D. 1999 Mol.Immunol. 36 423 10449095
3cpp Crystal structure of the carbon monoxide-substrate-cytochrome P-450CAM ternary complex. Raag, R., Poulos, T.L. 1989 Biochemistry 28 7586 2611203
4cpp Crystal structures of cytochrome P-450CAM complexed with camphane, thiocamphor, and adamantane: factors controlling P-450 substrate hydroxylation. Raag, R., Poulos, T.L. 1991 Biochemistry 30 2674 2001355
6cpp
8cpp
5cp4 Understanding the role of the essential Asp251 in cytochrome p450cam using site-directed mutagenesis, crystallography, and kinetic solvent isotope effect. Vidakovic, M., Sligar, S.G., Li, H., Poulos, T.L. 1998 Biochemistry 37 9211 9649301
6cp4
5cpp The structural basis for substrate-induced changes in redox potential and spin equilibrium in cytochrome P-450CAM. Raag, R., Poulos, T.L. 1989 Biochemistry 28 917 2713354
7cpp

シトクロムp450についてさらに知りたい方へ

当記事を作成するに当たって用いた参考文献を以下に示します。

  • F. P. Guengerich 2001 Common and uncommon cytochrome p450 reactions related to metabolism and chemical toxicity. Chemical Research in Toxicology 14 611-650
  • P. Anzenbacher and E. Anzenbacherova 2001 Cytochromes p450 and metabolism of xenobiotics. Cellular and Molecular Life Sciences 58 737-747
  • F. P. Guengerich 1993 Cytochrome p450 enzymes. American Scientist 81 (Sept-Oct), 440-447



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2006-10-01 (last edited: 10 months ago)2016-09-09
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