推测在衬底结构与活性关系(SSAR)的细胞色素P450酶。
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史密斯哒,琼斯BC
推测在衬底结构与活性关系(SSAR)的细胞色素P450酶。
生物化学杂志。1992年12月1日,44 (11):2089 - 98。
- PubMed ID
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1472073 (在PubMed]
- 文摘
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这个简短回顾试图定义SSAR细胞色素P450的两个家庭。与P4502D催化能力是通过紧密离子绑定使酶高区域选择性。相比之下P4503A达到催化能力通过一个灵活的结合位点依靠疏水的力量,使化学脆弱的网站是新陈代谢的主要场所。一般来说,不同的绑定机制应该反映在酶,这样的基质P4502D P4503A的Km值应低于基质。P4502D可能因此,新陈代谢的途径催化了饱和在衬底浓度低于P4503A路线催化了。P4502D之间的明显差异和P4503A底物特异性带进细胞色素P450的关系管理其他家庭问题。我们对数据的分析表明,所涉及的其他主要形式,一般来说,在人类药物代谢P4502C9(可能2 c8和2 c10)。酶负责苯妥英的新陈代谢,甲苯磺丁脲、替尼酸[4]、萘普生、布洛芬、双氯芬酸[38],7-hydroxylation S-warfarin[39]和三角洲的7-hydroxylation 1-tetrahydrocannabinol [40]。这些化合物都有强烈的氢键[4]领域形成潜在的(图8),所有5-10A远离的新陈代谢。此外萘普生的羧酸功能,布洛芬和双氯芬酸(pKa 4.5)和甲苯磺丁脲的磺酰脲类(pKa 5.4)呈现电离的化合物在生理博士电离集团网站的定位7-11A新陈代谢。 It is likely, therefore, that hydrogen bonding and possibly ion-pair interactions play a major role in determining the SSAR of the P4502C isoenzymes. These interactions would suggest that the P4502C enzymes are analogous to P4502D rather than P4503A. In this regard it is noteworthy that P4502C9 is selectively and potently inhibited by sulfaphenazole (IC50 of 0.6 microM), a compound that is structurally related (Fig. 8) to the substrates in terms of potential hydrogen bonding regions [4, 41]. Simplistically we suggest that the SSAR of the various P450 enzymes ranges from the highly selective enzymes dealing with endogenous substrates, through the enzymes metabolising exogenous substrates with narrow substrate structure requirements such as P4502D to P4503A with its broad substrate structure range. It would seem logical that animals and humans would evolve such combinations of isoenzymes to deal with the vast array of exogenous xenobiotics.
DrugBank数据引用了这篇文章
- 药物酶
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药物 酶 类 生物 药理作用 行动 心得乐 细胞色素P450 2 d6 蛋白质 人类 未知的底物抑制剂细节 - 药物反应
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反应 细节
