Elucidation of structure-properties relationships in carboxylesterases.

在这个后基因组时代，对蛋白质序列-结构-性质关系的理解从未如此重要。目前，蛋白质纯化和表征的速度大大超过了存储在各种数据库中的DNA序列的数量，我们无法利用基因组序列信息预测蛋白质的行为，这大大减缓了发现的步伐。通过提高我们对控制酶性质的序列基序或特征的理解，我们将允许从基因组数据中准确提取蛋白质特征信息，从而加速各个领域的创新，如医学研究、营养、药物合成和一些水基工业过程。这就是为什么包括我们在内的几个实验室继续对蛋白质序列编码信息进行基础研究的原因。对羧酸酯酶（“脂肪酶”）的研究表明，这种酶可能非常适合于实现我们的基本目标，即阐明蛋白质的序列-结构-性质关系。由于它们的亲缘关系，芽孢杆菌羧酸酯酶具有非常相似的三维结构，但在它们的性质上却表现出很大的差异。

The understanding of sequence-structure-properties relationships in proteins has never been so important as in this post-genomic era. Currently, protein purification and characterisation is dramatically outpaced by the volume of DNA sequence deposited in various databanks, and our inability to predict protein behaviour using genome sequence information drastically slows the pace of discovery. By improving our understanding of sequence motifs or signatures that control enzymatic properties, we will allow the accurate extraction of protein character information from genomic data, and thus accelerate innovation in various fields, such as medical research, nutrition, drug synthesis and a number of water-based industrial processes. This is why several labs, including ours, continue their basic research on protein sequence encoded information. Investigation of carboxylesterases ("lipase") revealed that such enzymes might be well suited for achieving our fundamental goal which is the elucidation of sequence-structure-properties relationships in proteins. Because of their relatedness, Bacillacae carboxylesterases share a very similar 3D organisation, yet display large differences in their properties. Our short-term objectives are to identify putative sequence motifs that might be associated with a specific property of an individual carboxylesterase. Then related carboxylesterases will be modified by genetic means in order to demonstrate the relationship between the putative motif and the enzyme property. For that an array of molecular biology and bioinformatics tools will be used, along as robotised high-throughput enzymatic analyses under various conditions. Our long term objective is to elucidate sequence-structure-properties relationships in order to improve our ability to predict features of putative carboxylesterases, and more generally lipases, suggested by genomic annotation. Further, with this new knowledge, we hope to help protein engineers in the development of customised enzymes for novel industrial applications.