Reconstruction of Two-Billion-Year-Old Enzyme Solves Mystery

Molecular biologists and bioinformatics scientists working at One Direction

The focus of the study was on a type of enzyme famed as tRNA nucleotidyltransferases, that links three building blocks of nucleotides in the C-C-A sequence to small RNAs named transfer RNAs. To supply amino acids for proteins inside the cells. Directed by Professors Mario Mörl and Sonja Prohaska, the investigation team managed to use phylogenetic restorations to rebuild a possible ancestral enzyme that dwells in bacteria for about Two billion years equal to a nowadays bacterial enzyme.

The team found out that the two enzymes were the same but presented clear differences in their functioning. In the past, scientists were unable to comprehend why nowadays´s enzymes often stopped working. The study demonstrated an evolutionary benefit, which amazed biochemists for years.

The predecessor enzyme is progressive and works frequently non-stop. However, from time to time correctly added nucleotide building blocks are reduced. The findings demonstrate that enzyme restorations can offer a clear perception right into the development and many other interrogations regarding today’s enzyme. Add to that, it manifests the great meaning of the interaction between bioinformatics and biochemistry. That involves lab testing and computer calculations.

Shimmying into the past by Drawing Relation

Bacteria create developmental phylogenetic trees by gene sequence. Starting with the nowadays huge range of organisms in a species tree, the path of unique genes’ development may be reconstructed by seeking their state of relatedness and connections. Lastly, examine them back to a shared ancestor. The restoration is a three-step procedure. That gives a much clear vision of the developmental journey of the genes.

The sequence can be utilized subsequently to determine their provenience. The very exact gene pattern coding for the old enzyme is later on acquainted with lab bacteria to guarantee they develop the wanted protein. The enzyme is later checked in more detail and compared with the existing ones. “The big finding happened after the lab got the great notice that the restored enzyme was able to perform C-C-A addition on a wider variety of climate conditions different from the recent one,” Sonja Prohaska remembers.

Evolutionary optimization: Pauses in activity boost efficiency

Enzymes, as organisms, experiment with optimization through evolution. The performance of an enzyme in catalyzing a reaction improves when it can strongly stick to its substrate. The predecessor enzyme that was reconstructed exhibited this particularity as it firmly held on to its substrate, the tRNA, and linked the three C-C-A nucleotides without releasing them, resulting in a bigger efficiency in performing the accelerating function.

In contrast, modern tRNA nucleotidyl transferases work in stages with intervals of pauses during which they repeatedly release their substrate. This kind of function is known as distributive. Despite this, modern enzymes are quicker and more efficient than their ancestral predecessors, which left scientists impressed. The reason why modern enzymes repeatedly deliver their substrate lies in the occurrence of a reverse reaction in which the enzyme removes the incorporated nucleotides. Unlike the ancestral enzyme, whose strong binding to the substrate leads to subsequent removal, contemporary enzymes prevent the reverse reaction almost entirely by releasing the substrate. This allows them to work with greater efficiency compared to their predecessors.

“Mario Mörl said that they have finally been able to address an explanation for the reason why modern tRNA nucleotidyl transferases work with so much efficiency regardless of their allocatable activity”.

“The group was taken by complete amazement by the discovery. They had not anticipated such an outcome. The question had been on their minds for the past 20 years, and they were finally able to answer it with the help of bioinformatics reconstruction methods. The cooperation between bioinformatics and biochemistry has existed in Leipzig for lots of years. It has proven not for the first time to be a great advantage for both sides.”

Read the original article on Scitech Daily.

Read more: Genome Study Finds Unexpected Variation in a Fundamental RNA Gene