Calvanese Luisa, Falcigno Lucia, Squeglia Flavia, D'Auria Gabriella, Berisio Rita
CIRPeB, University of Naples Federico II, via Mezzocannone 16, 80134, Naples, Italy.
Department of Pharmacy, University of Naples "Federico II", via Mezzocannone 16, 80134, Naples, Italy.
Curr Med Chem. 2017 Nov 24;24(36):4038-4056. doi: 10.2174/0929867324666170216112746.
Penicillin binding proteins (PBPs) and Serine Threonine kinases (STPKs) are two classes of bacterial enzymes whose involvement in a series of vital processes in bacterial growth and division is well assessed. Many PBPs and STPKs show linked an ancillary domain named PASTA, whose functional role is not completely deciphered so far. It has been proposed that PASTAs are sensor modules that by binding opportune ligands (i.e. muropeptides) activate the cognate proteins to their functions. However, based on recent data, the sensor annotation sounds true for PASTA from STPKs, and false for PASTA from PBPs.
Different PASTA domains, belonging or not to different protein classes, sharing or not appreciable sequence identities, always show identical folds. This survey of the structural, binding and dynamic properties of PASTA domains pursues the reasons why identical topologies may turn in different roles.
Amino acid compositions, total charges and distribution of the hydrophobic/hydrophilic patches on the surface, significantly vary among PASTAs from STPKs and PBPs and appear to correlate with different functions. A possible criterion to discriminate between PASTA modules of STPKs or PBPs solely based on their sequences is proposed. Possibly reflecting different species as well as functional roles and evolutionary profile, our routine represents a fast even though approximate method to distinguish between PASTA belonging to different classes.
青霉素结合蛋白（PBPs）和丝氨酸苏氨酸激酶（STPKs）是两类细菌酶，它们在细菌生长和分裂的一系列重要过程中的作用已得到充分评估。许多PBPs和STPKs显示出一个名为PASTA的辅助结构域，其功能作用至今尚未完全破译。有人提出，PASTA是传感器模块，通过结合合适的配体（即胞壁肽）激活同源蛋白发挥其功能。然而，根据最近的数据，传感器注释对于STPKs的PASTA来说似乎是正确的，而对于PBPs的PASTA来说则是错误的。
不同的PASTA结构域，无论是否属于不同的蛋白质类别，是否具有明显的序列同一性，总是显示出相同的折叠结构。本研究对PASTA结构域的结构、结合和动力学特性进行了探讨，以寻找相同拓扑结构可能发挥不同作用的原因。
STPKs和PBPs的PASTA在氨基酸组成、总电荷以及表面疏水/亲水斑块的分布上存在显著差异，并且似乎与不同的功能相关。提出了一种仅基于序列来区分STPKs或PBPs的PASTA模块的可能标准。我们的方法可能反映了不同的物种以及功能作用和进化特征，它是一种快速但近似的方法，用于区分属于不同类别的PASTA。
