title: A role for [Fe4S4] clusters in tRNA recognition--a theoretical study.
abstract: Over the past several years, structural studies have led to the unexpected discovery of iron-sulfur clusters in enzymes that are involved in DNA replication/repair and protein biosynthesis. Although these clusters are generally well-studied cofactors, their significance in the new contexts often remains elusive. One fascinating example is a tryptophanyl-tRNA synthetase from the thermophilic bacterium Thermotoga maritima, TmTrpRS, that has recently been structurally characterized. It represents an unprecedented connection among a primordial iron-sulfur cofactor, RNA and protein biosynthesis. Here, a possible role of the [Fe4S4] cluster in tRNA anticodon-loop recognition is investigated by means of density functional theory and comparison with the structure of a human tryptophanyl-tRNA synthetase/tRNA complex. It turns out that a cluster-coordinating cysteine residue, R224, and polar main chain atoms form a characteristic structural motif for recognizing a putative 5' cytosine or 5' 2-thiocytosine moiety in the anticodon loop of the tRNA molecule. This motif provides not only affinity but also specificity by creating a structural and energetical penalty for the binding of other bases, such as uracil.
authors.affiliation: Laboratorium für Physikalische Chemie, ETH Zurich, Vladimir-Prelog-Weg 2, 8093 Zurich, Switzerland martin.stiebritz@phys.chem.ethz.ch.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Stiebritz
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000926:Anticodon / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D020029:Base Pairing; D020134:Catalytic Domain; D003062:Codon / Q000737:chemistry; D003198:Computer Simulation; D017124:Conserved Sequence; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D012364:RNA, Transfer, Trp / Q000737:chemistry*; D013816:Thermodynamics; D020124:Thermotoga maritima / Q000201:enzymology; D014369:Tryptophan-tRNA Ligase / Q000737:chemistry*
chemical_list: D000926:Anticodon; D001426:Bacterial Proteins; D003062:Codon; D007506:Iron-Sulfur Proteins; D012364:RNA, Transfer, Trp; D014369:Tryptophan-tRNA Ligase
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