Function
Lysyl-tRNA synthetase (LysS) is a member of the class II aminoacyl-tRNA synthetases and catalyses the specific aminoacylation of tRNA(Lys). There are two different proteins that code for lysyl-tRNA synthase, LysS and LysU. The LysS is expressed under normal contionds, where the LysU is overexpressed in conditions like high temperature, anaerobiosis, low external pH, or the presence of leucine. [1] The source organism comes from Escherichia coli. The LysS is a protein that plays an important role in the translation of the genetic sequence. The LysS aids in an accurate translation of the mRNA. [2]
Relevance
A defect in the translation of the genetic material from LysS would impact the functionality of the protein. The LysS gene has been determined to coincide with the HerC gene. Through overproducing the HerC gene a rapid mass scale of Lysyl-tRNA synthase can be made. Lysyl-tRNA synthase has been thought to be used for a drug target that lead to drug discovery capable of clearing parasites from mouse models with malaria and cryptosporidiosis infection. [3]
Disease
A mutation in the LysS has shown to have played a role in the reduction of the outer membrane vesiculation. [4] With the overproduction of the HerC a mutation could happen causing macrocephaly.
Structural highlights
The first interaction that leads to a reorganization of the active site is from the binding of the α amino group from the lysine and the carbonyl oxygen of Gly216. The second interaction is between the carboxylate group and the side chin of Arg262. The interactions of both lead to the
. When reorganizing the active sites, the ordering of two loops (residues 215-217 and 444-455) are formed. The change in the conformation of residues 393-409 is another result from the reorganization. The final change is the rotation of a 4-helix bundle (located between motif 2 & 3) by 10°. The results of these interactions is the closing up of active site upon lysine binding.[5]
