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参考文献:Engineered Thermoplasma Acidophilum Factor F3 Mimics Human Aminopeptidase N (Apn) As A Target For Anticancer Drug Development
标题:Engineered Thermoplasma Acidophilum Factor F3 Mimics Human Aminopeptidase N (Apn) As A Target For Anticancer Drug Development
摘要:Human Aminopeptidase N (Hapn) Is An Appealing Objective For The Development Of Anti-Cancer Agents. The Absence Of Mammalian Apn Experimental Structure Negatively Impinges Upon The Progression Of Structure-Based Drug Design. Tricorn Interacting Factor F3 (Factor F3) From Thermoplasma Acidophilum Shares 33% Sequence Identity With Hapn. Engineered Factor F3 With Two Point Directed Mutations Resulted In A Protein With An Active Site Identical To Hapn. In The Present Work,The Engineered Factor F3 Has Been Co-Crystallized With Compound D24,A Potent Apn Inhibitor Introduced By Our Lab. Such A Holo-Form Experimental Structure Helpfully Insinuates A More Bulky Pocket Than Bestatin-Bound Escherichia Coli Apn. This Evidence Discloses That Compound D24 Targetting The Structure Of E. Coli Apn Cannot Bind To The Activity Cleft Of Factor F3 With High Affinity. Thus,There Is A Potential Risk Of Inefficiency To Design Hapn Targeting Drug While Using E. Coli Apn As The Target Model. We Do Propose Here Now That Engineered Factor F3 Can Be Employed As A Reasonable Alternative Of Hapn For Drug Design And Development. (C) 2011 Elsevier Ltd. All Rights Reserved.
Doi:10.1016/j.Bmc.2011.03.028