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作为脱氨酶底物的腺苷和胞苷的构象锁定碳环核苷的对比行为。

Contrasting behavior of conformationally locked carbocyclic nucleosides of adenosine and cytidine as substrates for deaminases.

作者信息

Marquez Victor E, Schroeder Gottfried K, Ludek Olaf R, Siddiqui Maqbool A, Ezzitouni Abdallah, Wolfenden Richard

机构信息

Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):614-32. doi: 10.1080/15257770903091904.

Abstract

In addition to the already known differences between adenosine deaminase (ADA) and cytidine deaminase (CDA) in terms of their tertiary structure, the sphere of Zn(+2) coordination, and their reverse stereochemical preference, we present evidence that the enzymes also differ significantly in terms of the North/South conformational preferences for their substrates and the extent to which the lack of the O(4') oxygen affects the kinetics of the enzymatic deamination of carbocyclic substrates. The carbocyclic nucleoside substrates used in this study have either a flexible cyclopentane ring or a rigid bicyclo[3.1.0]hexane scaffold.

摘要

除了已知的腺苷脱氨酶(ADA)和胞苷脱氨酶(CDA)在三级结构、Zn(+2)配位范围以及相反的立体化学偏好方面存在差异外,我们还提供了证据表明,这两种酶在底物的南北构象偏好以及O(4')氧的缺失对碳环底物酶促脱氨动力学的影响程度方面也存在显著差异。本研究中使用的碳环核苷底物具有灵活的环戊烷环或刚性的双环[3.1.0]己烷骨架。

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