SPARC: Structural properties associated with residue constraints.
SPARC: Structural properties associated with residue constraints.
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DOI：
10.1016/j.csbj.2022.04.005
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发表时间：
2022
影响因子：
6
通讯作者：
中科院分区：
文献类型：
--
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SPARC通过从结构上表征蛋白质序列约束，促进了关于潜在生化机制的可信假说的产生。这种限制表现为功能相关亚群中的残基共同保守，表现为微妙的成对相关性(即直接偶联)，以及这些序列特征之间的相关性或与结构特征的相关性。SPARC执行三种类型的分析。首先，基于成对的序列相关性，它估计了不同构象和同分体接触的生物学相关性，如这里所示的死亡区域。其次，它估计了直接耦合残基对之间的对应关系和异二聚体界面上的相互作用的统计意义。第三，给定分子动力学模拟结构，它描述了受约束残基之间或这些残基与配体之间的相互作用，这些相互作用：(A)在模拟过程中稳定地保持；(B)经历与其他受约束残基的相互作用的相关形成和/或中断；或(C)在替代相互作用之间切换。我们对两个同源六聚体复合体进行了说明：细菌增强子结合蛋白(BEBP)NtrC1，它通过含有DNA54的重塑RNA聚合酶激活转录，以及DNAB解旋酶，它在细菌复制叉处打开σ。基于Ntrc1的分析，我们假设了抑制三磷酸腺苷水解酶直到腺苷二磷酸从相邻亚基释放，以及三磷酸腺苷水解酶与σ54结合环的重组的可能机制。基于DNAB的分析，我们假设DNAB通过每四个碱基翻转一次并将其插入亚基之间的空腔来“抓住”单链DNA，而DNAB特异性谷氨酰胺残基的翻转触发了ATP水解。
SPARC facilitates the generation of plausible hypotheses regarding underlying biochemical mechanisms by structurally characterizing protein sequence constraints. Such constraints appear as residues co-conserved in functionally related subgroups, as subtle pairwise correlations (i.e., direct couplings), and as correlations among these sequence features or with structural features. SPARC performs three types of analyses. First, based on pairwise sequence correlations, it estimates the biological relevance of alternative conformations and of homomeric contacts, as illustrated here for death domains. Second, it estimates the statistical significance of the correspondence between directly coupled residue pairs and interactions at heterodimeric interfaces. Third, given molecular dynamics simulated structures, it characterizes interactions among constrained residues or between such residues and ligands that: (a) are stably maintained during the simulation; (b) undergo correlated formation and/or disruption of interactions with other constrained residues; or (c) switch between alternative interactions. We illustrate this for two homohexameric complexes: the bacterial enhancer binding protein (bEBP) NtrC1, which activates transcription by remodeling RNA polymerase (RNAP) containing σ54, and for DnaB helicase, which opens DNA at the bacterial replication fork. Based on the NtrC1 analysis, we hypothesize possible mechanisms for inhibiting ATP hydrolysis until ADP is released from an adjacent subunit and for coupling ATP hydrolysis to restructuring of σ54 binding loops. Based on the DnaB analysis, we hypothesize that DnaB ‘grabs’ ssDNA by flipping every fourth base and inserting it into cavities between subunits and that flipping of a DnaB-specific glutamine residue triggers ATP hydrolysis.
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影响因子：
16
作者：
Bose, Daniel;Pape, Tillmann;Burrows, Patricia C.;Rappas, Mathieu;Wigneshweraraj, Siva R.;Buck, Martin;Zhang, Xiaodong
通讯作者：
Zhang, Xiaodong
影响因子：
64.5
作者：
Hopf TA;Colwell LJ;Sheridan R;Rost B;Sander C;Marks DS
通讯作者：
Marks DS
DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
影响因子：
--
作者：
Fisher, RA
通讯作者：
Fisher, RA
影响因子：
5.7
作者：
Huang, WJ;Jia, J;Lindqvist, Y
通讯作者：
Lindqvist, Y