***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature
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Input: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Output:  When species evolve, their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment. In this scenario, unrelated genes can convergently evolve to produce proteins with the same molecular function, termed “functionally analogous.” A quantitative determination of the reaction similarities among functionally analogous enzymes could provide insight about the different structural solutions nature has used to evolve similar catalysts. Bond changes between substrates and products, and between successive reaction intermediates, were used to compare the reactions catalyzed and the mechanisms of catalysis for 95 pairs of functionally analogous enzymes. Less than half of the reactions catalyzed by unrelated enzymes, but defined as similar by the Enzyme Commission (EC) classification, are similar in terms of bond changes, suggesting that this classification often fails to capture quantitative differences between many enzyme reactions. Furthermore, we addressed for the first time whether the chemical mechanisms by which similar overall reactions are achieved in functional analogs are also similar. We conclude that convergence of reaction is often accompanied by convergence of chemical mechanism. These results will be useful for classifying enzymes, guiding functional annotation of newly determined enzyme sequences and structures and for informing the engineering of enzymes with new functions.

Input:  Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.


Output:

In recent years it has become clear that complex developmental processes are not regulated by single transcription factors but rather by combinations of transcription factors that interact in intricate regulatory networks. Here, we analyze the regulatory network that drives terminal differentiation of oligodendrocytes, the cells of the vertebrate central nervous system that form myelin and thereby guarantee rapid saltatory conduction. We show that the transcription factor Myrf is directly activated by the transcription factor Sox10, and map a Sox10-responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. We then go on to show that once induced, Myrf physically interacts and functionally cooperates with its inducer Sox10 to activate myelin genes arguing that the two jointly drive terminal differentiation of oligodendrocytes. With this study we define an essential module in the myelin-specific regulatory network in the central nervous system. By comparing this module with the corresponding module in Schwann cells of the peripheral nervous system which consists of Sox10 and the Krox20 transcription factor we furthermore conclude that myelination in the two compartments of the vertebrate nervous system is regulated by similarly organized, but differentially implemented regulatory networks.
