环核苷酸结合 GAF 结构域来自磷酸二酯酶：结构和机制见解。
Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights.
机构信息
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Pfizer, Inc., PGRD, Groton, 558 Eastern Point Road, Groton, CT 06340, USA.
出版信息
Structure. 2009 Dec 9;17(12):1551-1557. doi: 10.1016/j.str.2009.07.019.
Abstract
GAF domains regulate the catalytic activity of certain vertebrate cyclic nucleotide phosphodiesterases (PDEs) by allosteric, noncatalytic binding of cyclic nucleotides. GAF domains arranged in tandem are found in PDE2, -5, -6, -10, and -11, all of which regulate the cellular concentrations of the second messengers cAMP and/or cGMP. Nucleotide binding to GAF domains affects the overall conformation and the catalytic activity of full-length PDEs. The cyclic nucleotide-bound GAF domains from PDE2, -5, -6, and -10 all adopt a conserved fold but show subtle differences within the binding pocket architecture that account for a large range of nucleotide affinities and selectivity. NMR data and details from the structure of full-length nucleotide-free PDE2A reveal the dynamic nature and magnitude of the conformational change that accompanies nucleotide binding. The discussed GAF domain structures further reveal differences in dimerization properties and highlight the structural diversity within GAF domain-containing PDEs.
摘要
GAF 结构域通过环核苷酸的别构、非催化结合来调节某些脊椎动物环核苷酸磷酸二酯酶（PDEs）的催化活性。串联排列的 GAF 结构域存在于 PDE2、-5、-6、-10 和 -11 中，它们都调节第二信使 cAMP 和/或 cGMP 的细胞浓度。核苷酸与 GAF 结构域的结合会影响全长 PDE 的整体构象和催化活性。来自 PDE2、-5、-6 和 -10 的结合环核苷酸的 GAF 结构域都采用保守的折叠方式，但在结合口袋结构内存在细微差异，这些差异解释了核苷酸亲和力和选择性的广泛范围。NMR 数据和全长无核苷酸 PDE2A 的结构细节揭示了伴随核苷酸结合的构象变化的动态性质和幅度。所讨论的 GAF 结构域结构进一步揭示了二聚化性质的差异，并突出了包含 GAF 结构域的 PDE 中的结构多样性。
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