3LD6
Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with ketoconazole
「3I3K」から置き換えられました3LD6 の概要
エントリーDOI | 10.2210/pdb3ld6/pdb |
関連するPDBエントリー | 3JUS 3JUV |
関連するBIRD辞書のPRD_ID | PRD_900012 |
分子名称 | Lanosterol 14-alpha demethylase, Cycloheptakis-(1-4)-(alpha-D-glucopyranose), PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total) |
機能のキーワード | cytochrome p450, sterol 14alpha-demethylase, ketoconazole, structural genomics, structural genomics consortium, sgc, alternative splicing, cholesterol biosynthesis, endoplasmic reticulum, heme, iron, lipid synthesis, membrane, metal-binding, microsome, monooxygenase, nadp, oxidoreductase, polymorphism, steroid biosynthesis, sterol biosynthesis, transmembrane |
由来する生物種 | Homo sapiens (human) |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 110140.77 |
構造登録者 | Strushkevich, N.,Tempel, W.,MacKenzie, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Weigelt, J.,Park, H.,Structural Genomics Consortium (SGC) (登録日: 2010-01-12, 公開日: 2010-02-02, 最終更新日: 2023-09-06) |
主引用文献 | Strushkevich, N.,Usanov, S.A.,Park, H.W. Structural basis of human CYP51 inhibition by antifungal azoles. J.Mol.Biol., 397:1067-1078, 2010 Cited by PubMed Abstract: The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B' helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51. PubMed: 20149798DOI: 10.1016/j.jmb.2010.01.075 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.8 Å) |
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