水分子活性位点和衬底羟基氧活化的细胞色素P450 158 a2:一个新的质子转移的机制。
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赵B Guengerich FP Voehler M,沃特曼先生
水分子活性位点和衬底羟基氧活化的细胞色素P450 158 a2:一个新的质子转移的机制。
J生物化学杂志。2005年12月23日,280 (51):42188 - 97。Epub 2005 10月20。
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16239228 (在PubMed]
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x射线晶体结构的CYP158A2(赵,B。、Guengerich f P。Bellamine,。、羊肉、d . C。Izumikawa, M。Lei, L。、Podust l . M。Sundaramoorthy, M。Reddy, l . M。凯利,s . L。Kalaitzis, j。Stec D。Voehler, M。Falck, j . R。摩尔,b。什,T。和沃特曼,m . r .(2005)生物。化学,280,11599 - 11607),一个18岁的细胞色素P450 (CYP)基因在无公害coelicolor,下令水分子活性位点(WAT505, WAT600, WAT640)和羟基的衬底flaviolin提出了参与质子转移在这个单氧酶和氧的乳沟。调查他们的角色在催化,我们研究了基质的晶体结构模拟与铁(2-hydroxy-1 4-naphthoquinone)复杂CYP158A2(2.15)和flaviolin亚铁dioxygen-bound CYP158A2复杂(1.8)。对2-hydroxy-1催化活性,4-naphthoquinone与flaviolin小于大约70倍。 In the ferrous dioxygen-bound flaviolin complex, the three water molecules in the ferric flaviolin complex still occupy the same positions and form hydrogen bonds to the distal dioxygen atom. These findings suggest that CYP158A2 utilizes substrate hydroxyl groups to stabilize active site water and further assist in the iron-linked dioxygen activation. A continuous hydrogen-bonded water network connecting the active site to the protein surface (bulk solvent) not present in the other two ferrous dioxygen-bound P450 structures (CYP101A1/P450cam and CYP107A1/P450eryF) is proposed to participate in the proton-delivery cascade, leading to dioxygen bond scission. This ferrous-dioxygen structure suggests two classes of P450s based on the pathway of proton transfer, one using the highly conserved threonine in the I-helix (CYP101A1) and the other requiring hydroxyl groups of the substrate molecules either directly transferring protons (CYP107A1) or stabilizing a water pathway for proton transfer (CYP158A2).