User:Khadar Abdi/Sandbox1
From Proteopedia
(Difference between revisions)
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== Structural highlights== | == Structural highlights== | ||
| - | As mentioned earlier, TARS is homodimer protein found in two forms of a cell, mitochondrial and cytoplasmic. Most of the structures seen will primarly be bacterial cytoplasmic. The protein is mainly classified as a alpha beta protein in both bacteria and eukaryotic cells<ref>PMID:23362938</ref>. Each chain is composed of 4 domain classified by SCOP: a N1 domain, a N2 domain, a catalytic domain and an anti-codon domain<ref>PMID:12875846</ref>. | + | As mentioned earlier, TARS is homodimer protein found in two forms of a cell, mitochondrial and cytoplasmic. Most of the structures seen will primarly be bacterial cytoplasmic. The protein is mainly classified as a alpha beta protein in both bacteria and eukaryotic cells<ref>PMID:23362938</ref>. Each chain is composed of 4 domain classified by SCOP: <scene name='78/786634/Highlighted_structure_of_tars/2'>a N1 domain, a N2 domain, a catalytic domain and an anti-codon domain</scene><ref>PMID:12875846</ref>. |
===N-terminus (Residue 1-241)=== | ===N-terminus (Residue 1-241)=== | ||
| - | The N1-Domain and N-2 domain is the found in the N-terminus of the TARS enzyme chain. Specific N1 is found from 1-62 residue while N2 domain is found from | + | The <scene name='78/786634/Tgs-domain/2'>N1-Domain</scene> and <scene name='78/786634/Editing_domain/1'>N-2 domain</scene> is the found in the N-terminus of the TARS enzyme chain. Specific N1 is found from 1-62 residue while N2 domain is found from 63-241 residue(PDB: [[1TJE]]). Although located in neighboring regions, the N1-domain and N2-domain deviate dramatically from one another. Structurally, N1-domain has a TGS-fold (short for TARS, GTPase, Spo1 domain as their the most common proteins that present this fold)<ref>PMID:10447505</ref> which has 3 antiparallel beta sheets interacting with an alpha helix causing a formation of roll-like structure (similar to the description by Cath: Ubiquitin-like roll)<ref>http://www.rcsb.org/pdb/explore/macroMoleculeData.do?structureId=1TJE</ref>. The structure has no known function but it is pronounced structure found common within TARS. |
| - | This is the opposite of the N2-domain, or sometimes called TARS additional domain. This is ironic as this addition is very important for proofreading TARS activity<ref>PMID:15525511</ref>. TARS N2-domain is described as 2-layer alpha-beta sandwich comprised of mostly alpha helices. Interesting enough, the superfamily of this motif is found to be TARS and Alanyl-tRNA synthetase common domain. This domain function similar by discriminating Threonine and Alanine from Serine amino acid (Ser) as serine is similar structure to both amino acids. The editing domain functions first by moving Ser bound tRNA-Thr from the catalytic domain to the editing site by breaking the bonds nucleotide A73, C74, and C75 from the catalytic site allowing the acceptor arm of tRNA-Thr to flip to the editing domain of S12-S13 site. Research on editing hydrolysis propose that residue Tyr 103 plays an important role of guiding acceptor arm towards the editing domain. The Ser bound to tRNA is hydrolzed by a water molecule, interacting with His73, acting as a nucleophile to the alpha carbon of serine, follow by protonation by a 2nd water molecule interacting with carbonyl of Met181 and amide side chain Lys156. The fidility mechanism of AA-tRNA binding is much similar to alanine tRNA-ligase found in the C-terminus as they share 40% similarity in residues. The subtle difference of the isoforms mitochondrial TARS from cytoplasmic TARS appears in editing as the mitochondrial TARS doesn't have N2-domain and requires interaction to hydrolyze serine <ref>PMID:22773845</ref>. | + | This is the opposite of the N2-domain, or sometimes called TARS additional domain. This is ironic as this addition is very important for proofreading TARS activity<ref>PMID:15525511</ref>. TARS N2-domain is described as 2-layer alpha-beta sandwich comprised of mostly alpha helices. Interesting enough, the superfamily of this motif is found to be TARS and Alanyl-tRNA synthetase common domain. This domain function similar by discriminating Threonine and Alanine from Serine amino acid (Ser) as serine is similar structure to both amino acids. The editing domain functions first by moving Ser bound tRNA-Thr from the catalytic domain to the <scene name='78/786634/Editing_domain_residues/1'>editing site</scene> by breaking the bonds nucleotide A73, C74, and C75 from the catalytic site allowing the acceptor arm of tRNA-Thr to flip to the editing domain of S12-S13 site. Research on editing hydrolysis propose that residue Tyr 103 plays an important role of guiding acceptor arm towards the editing domain. The Ser bound to tRNA is hydrolzed by a water molecule, interacting with His73, acting as a nucleophile to the alpha carbon of serine, follow by protonation by a 2nd water molecule interacting with carbonyl of Met181 and amide side chain Lys156. The fidility mechanism of AA-tRNA binding is much similar to alanine tRNA-ligase found in the C-terminus as they share 40% similarity in residues. The subtle difference of the isoforms mitochondrial TARS from cytoplasmic TARS appears in editing as the mitochondrial TARS doesn't have N2-domain and requires interaction to hydrolyze serine <ref>PMID:22773845</ref>. |
===Catalytic Domain (Residue 243-532)=== | ===Catalytic Domain (Residue 243-532)=== | ||
| - | As the name implies, the catalytic domain is the main area of protein activity. This domain is linked with N2-Domain of TARS by a alpha helix, or a linker helix. The domain is architecturally described as a 2-layer alpha beta sandwhich. The importance of the domain is that it has 3 sites of binding: motif 1: ordering loop; motif 2 loop, Motif 3: threonine loop, and motif 4: ATP binding. The main important residues within in the caatalytic site include: Tyr ,Arg , Arg , His309 | + | As the name implies, the catalytic domain is the main area of protein activity. This domain is linked with N2-Domain of TARS by a alpha helix, or a linker helix (residue 225-242). The domain is architecturally described as a 2-layer alpha beta sandwhich. The importance of the domain is that it has 3 sites of binding: motif 1: ordering loop; motif 2 loop, Motif 3: threonine loop, and motif 4: ATP binding. The main important residues within in the caatalytic site include: Tyr ,Arg , Arg , His309 |
| - | What is interesting about the motif 1 is that it is highly dependent on the presence of zinc divalent ion (Zn2+). The Zn2+ plays a huge salt bridge role for connecting Thr and TARS itself <ref>PMID:10319817</ref>. Zn2+ binds to TARS 2 histidine and 1 cysteine | + | What is interesting about the motif 1 is that it is highly dependent on the presence of zinc divalent ion (Zn2+). The Zn2+ plays a huge salt bridge role for connecting Thr and TARS itself <ref>PMID:10319817</ref>. Zn2+ binds to TARS' 2 histidine and 1 cysteine residues and a water molecule (for ''S. aureus it was Cys336, His387, and His571; versus ''E. coli.'' was Cys334, His385, and His511) and the Thr amino acid's hydroxyl side chain and N-terminus. This prevents similar molecules lacking hydroxyl groups such as valine. Asides Zn2+, Mg2+ is also necessary for |
===Anti-Codon Domain(Residue 533-645)=== | ===Anti-Codon Domain(Residue 533-645)=== | ||
| - | + | Lastly, there is the C-terminus domain of the TARS protein, otherwise known as the anticodon-domain. This alpha-beta region is conserved through most aaRs class 2 molecules but have a specificity towards binding to tRNA-thr. This domain has a Rossmann-fold, which is 3-layer sandwhich fold necessary for binding of nucleotides, in this case tRNA nucleotides. This domain recognize and bind to tRNA-thr major groove containing BGU anticodon consensus sequence (B: Guanine, Cytosine, or Uracil). Although tRNA binding is important to hold on for aminoacylation, this should not be confused with having any aminoacylation activity. | |
== Evolutionary related proteins == | == Evolutionary related proteins == | ||
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| + | <scene name='78/786634/Tars_conservation/1'>Representation of TARS ''S. Aureus'' conservation of amino acids</scene> | ||
==Disease Relevance== | ==Disease Relevance== | ||
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== List to available structures == | == List to available structures == | ||
===Bacterial=== | ===Bacterial=== | ||
| - | E coli: [[1qf6]] | + | ''E. coli'': [[1qf6]] |
| - | S. Aureus: [[1nyq]] | + | ''S. Aureus'': [[1nyq]] |
| - | Yeast: [[3ugt]] | + | Yeast (''Saccharomyces cerevisiae''): [[3ugt]] |
===Eukaryotic=== | ===Eukaryotic=== | ||
Revision as of 20:24, 1 May 2018
Threonyl-tRNA Synthetase/ligase
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