BECAS
LOPEZ Maria Belen
congresos y reuniones científicas
Título:
Bioinformatic analysis of Malate Thiokinase, a key enzyme in the Serine pathway for assimilation of C1 compounds and energy conversion
Autor/es:
MARIA BELEN LOPEZ; JAVIER MARCELO GONZÁLEZ
Reunión:
Jornada; Sociedad Argentina de Biofísica Biofísica en tiempos de COVID-19 : Primeras Jornadas Virtuales SAB 2020; 2020
Institución organizadora:
Sociedad Argentina de Biofísica
Resumen:
Climate change resulting from the accumulation of greenhouse gases is a matter ofglobal concern. A solution to this problem could be found in Synthetic Biology for thegeneration of artificial metabolic pathways using enzymes for assimilation of C1compounds of the Serine pathway present in bacteria of the genus Methylorubrum.Malate thiokinase (MTK) is a heterodimer (α and β subunits) whose family includes ATPcitratelyases and succinyl-CoA synthetases (SCS). It catalyzes the only phosphorylationstep at the substrate level of the Serine pathway, reversibly producing Malyl-CoA, PO43-and ADP from malate, CoA and ATP, the reaction direction depends on the relativeconcentrations of substrates and products. It is interesting due to its dual function,catalyzing a key step in the assimilation of C1 and having the important and unusualcapacity to exchange energy between CoA thioesters and adenylates.In order to infer the structural properties of MTK whose structure has not yet beensolved. The enzyme was examined structurally and phylogenetically using: homologymodeling, phylogenetic analysis and sequence similarity networks (SSN). The structuresmodeled for MTKα and MTKβ are acceptable since they presented r.m.s.d values close tozero and more than 90% of residues in favorable regions. SSNs for MTKα and MTKβ werecalculated for the Pfam family PF00549. Their sequences were retrieved from UniProt.The phylogenetic trees were generated with the maximum likelihood algorithm RAxMLwith automatic bootstop criterion. Homology modeling of the 3D structure of M.extorquens MTK was performed with Phyre2, MTKα showed a sequence similarity of 52 %with Sus scrofa SCS, while MTKβ showed a sequence similarity of 55 % with F. tularensisSCS. Looking at the distribution along the SSNs, it is clear that many sequences remainto be functionally characterized. Only 7 nodes have SwissProt descriptions and PDBstructures, and they are SCS enzymes, representing 7 out of 3,165 nodes (0.2%). MTKβsubunits are more conserved that MTKα subunits, as inferred from neighborhoodconnectivity analysis. Besides, genome neighborhood analysis indicates that MTKαβgenes are restricted to relatively few genera like Methylobacterium andHyphomicrobium.