两个氨基酸取代将鸟苷酸环化酶RetGC-1转变为腺苷酸环化酶。
Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase.
作者信息
Tucker C L, Hurley J H, Miller T R, Hurley J B
机构信息
Howard Hughes Medical Institute and Department of Biochemistry, Box 357370, University of Washington, Seattle, WA 98195, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 May 26;95(11):5993-7. doi: 10.1073/pnas.95.11.5993.
Abstract
Guanylyl cyclases (GCs) and adenylyl cyclases (ACs) have fundamental roles in a wide range of cellular processes. Whereas GCs use GTP as a substrate to form cGMP, ACs catalyze the analogous conversion of ATP to cAMP. Previously, a model based on the structure of adenylate cyclase was used to predict the structure of the nucleotide-binding pocket of a membrane guanylyl cyclase, RetGC-1. Based on this model, we replaced specific amino acids in the guanine-binding pocket of GC with their counterparts from AC. A change of two amino acids, E925K together with C995D, is sufficient to completely alter the nucleotide specificity from GTP to ATP. These experiments strongly validate the AC-derived RetGC-1 structural model and functionally confirm the role of these residues in nucleotide discrimination.
摘要
鸟苷酸环化酶（GCs）和腺苷酸环化酶（ACs）在广泛的细胞过程中发挥着重要作用。GCs利用GTP作为底物形成cGMP，而ACs催化ATP向cAMP的类似转化。此前，基于腺苷酸环化酶的结构建立了一个模型，用于预测膜鸟苷酸环化酶RetGC-1的核苷酸结合口袋的结构。基于该模型，我们将GC的鸟嘌呤结合口袋中的特定氨基酸替换为AC中的对应氨基酸。两个氨基酸的改变，即E925K和C995D一起，足以完全改变核苷酸特异性，从GTP变为ATP。这些实验有力地验证了源自AC的RetGC-1结构模型，并在功能上证实了这些残基在核苷酸识别中的作用。
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本文引用的文献
1
Raster3D Version 2.0. A program for photorealistic molecular graphics.光栅3D版本2.0。一个用于逼真分子图形的程序。
Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):869-73. doi: 10.1107/S0907444994006396.
2
Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 A resolution.噬菌体T7 DNA复制复合物的晶体结构，分辨率为2.2埃。
Nature. 1998 Jan 15;391(6664):251-8. doi: 10.1038/34593.
3
Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.腺苷酸环化酶催化结构域与Gsα.GTPγS复合物的晶体结构。
Science. 1997 Dec 12;278(5345):1907-16. doi: 10.1126/science.278.5345.1907.
4
Catalytic mechanism of the adenylyl and guanylyl cyclases: modeling and mutational analysis.腺苷酸环化酶和鸟苷酸环化酶的催化机制：建模与突变分析
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13414-9. doi: 10.1073/pnas.94.25.13414.
5
Domain-specific stabilization of photoreceptor membrane guanylyl cyclase by adenine nucleotides and guanylyl cyclase activating proteins (GCAPs).腺嘌呤核苷酸和鸟苷酸环化酶激活蛋白（GCAPs）对光感受器膜鸟苷酸环化酶的结构域特异性稳定作用。
Biochemistry. 1997 Sep 30;36(39):11995-2000. doi: 10.1021/bi971212k.
6
Calcium binding, but not a calcium-myristoyl switch, controls the ability of guanylyl cyclase-activating protein GCAP-2 to regulate photoreceptor guanylyl cyclase.钙结合而非钙-肉豆蔻酰开关控制鸟苷酸环化酶激活蛋白GCAP-2调节光感受器鸟苷酸环化酶的能力。
J Biol Chem. 1997 May 30;272(22):14327-33. doi: 10.1074/jbc.272.22.14327.
7
Structure of the adenylyl cyclase catalytic core.腺苷酸环化酶催化核心的结构。
Nature. 1997 Mar 20;386(6622):247-53. doi: 10.1038/386247a0.
8
A mutation of the atrial natriuretic peptide (guanylyl cyclase-A) receptor results in a constitutively hyperactive enzyme.心房利钠肽（鸟苷酸环化酶-A）受体的突变导致一种持续高活性的酶。
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):459-62. doi: 10.1073/pnas.94.2.459.
9
The membrane guanylyl cyclase, retinal guanylyl cyclase-1, is activated through its intracellular domain.
J Biol Chem. 1996 May 17;271(20):11646-51. doi: 10.1074/jbc.271.20.11646.
10
Guanylyl cyclase receptors.鸟苷酸环化酶受体
J Biol Chem. 1994 Dec 9;269(49):30741-4.
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