Residue propensities, discrimination and binding site prediction of adenine and guanine phosphates.
Residue propensities, discrimination and binding site prediction of adenine and guanine phosphates.
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DOI：
10.1186/1471-2091-12-20
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发表时间：
2011-05-13
期刊：
影响因子：
--
通讯作者：
Ahmad S
中科院分区：
文献类型：
--
作者：
Firoz A;Malik A;Joplin KH;Ahmad Z;Jha V;Ahmad S
腺嘌呤和鸟嘌呤磷酸参与许多生物过程，如细胞信号传导、代谢和酶辅因子功能。这些配体在蛋白质中的结合位点通常通过基于比对的搜索寻找先前已知的基序来检测。这可能会错过那些先前未表征过相似结合位点的位点，以及结合位点不遵循预定义基序所描述的规则的位点。此外，蛋白质如何在腺嘌呤和鸟嘌呤衍生物之间进行高特异性选择也很有趣。详细研究了AMP、GMP、ADP、GDP、ATP和GTP的残基偏好，并与环变体cAMP和cGMP进行了额外比较。我们还试图预测与这些核苷酸的信息来自本地序列和进化概况的残基相互作用。结果表明，单个碱基对特定核苷酸的偏好性存在细微差异，考虑到相邻环境和进化背景，可以建立成功的结合位点预测模型。在这项工作中，我们探索这些核苷酸的单个氨基酸倾向如何在这组核苷酸的亲和力和特异性中发挥作用。预计这将有助于确定腺嘌呤和鸟嘌呤磷酸的新的结合位点，特别是当一个已知的结合基序是不可检测的。
Adenine and guanine phosphates are involved in a number of biological processes such as cell signaling, metabolism and enzymatic cofactor functions. Binding sites in proteins for these ligands are often detected by looking for a previously known motif by alignment based search. This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif. Also, it is intriguing how proteins select between adenine and guanine derivative with high specificity. Residue preferences for AMP, GMP, ADP, GDP, ATP and GTP have been investigated in details with additional comparison with cyclic variants cAMP and cGMP. We also attempt to predict residues interacting with these nucleotides using information derived from local sequence and evolutionary profiles. Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed. In this work, we explore how single amino acid propensities for these nucleotides play a role in the affinity and specificity of this set of nucleotides. This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.
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