6h45

crystal structure of the human TGT catalytic subunit QTRT1 in complex with queuine

spinqualitylabelsall models 6h45, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6h45 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BR, CL, GLU, K, OCS, QEI, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TGT_HUMAN Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine) (PubMed:11255023, PubMed:20354154). Catalysis occurs through a double-displacement mechanism. The nucleophile active site attacks the C1' of nucleotide 34 to detach the guanine base from the RNA, forming a covalent enzyme-RNA intermediate. The proton acceptor active site deprotonates the incoming queuine, allowing a nucleophilic attack on the C1' of the ribose to form the product (By similarity).[UniProtKB:P28720][HAMAP-Rule:MF_03218] Publication Abstract from PubMed RNA modifications have been implicated in diverse and important roles in all kingdoms of life with over 100 of them present on tRNAs. A prominent modification at the wobble base of four tRNAs is the 7-deaza-guanine derivative queuine which substitutes the guanine at position 34. This exchange is catalyzed by members of the enzyme class of tRNA guanine transglycosylases (TGTs). These enzymes incorporate guanine substituents into tRNA(Asp), tRNA(Asn) tRNA(His), and tRNA(Tyr) in all kingdoms of life. In contrast to the homodimeric bacterial TGT, the active eukaryotic TGT is a heterodimer in solution, comprised of a catalytic QTRT1 subunit and a noncatalytic QTRT2 subunit. Bacterial TGT enzymes, that incorporate a queuine precursor, have been identified or proposed as virulence factors for infections by pathogens in humans and therefore are valuable targets for drug design. To date no structure of a eukaryotic catalytic subunit is reported, and differences to its bacterial counterpart have to be deducted from sequence analysis and models. Here we report the first crystal structure of a eukaryotic QTRT1 subunit and compare it to known structures of the bacterial TGT and murine QTRT2. Furthermore, we were able to determine the crystal structure of QTRT1 in complex with the queuine substrate. Crystal Structure of the Human tRNA Guanine Transglycosylase Catalytic Subunit QTRT1.,Johannsson S, Neumann P, Ficner R Biomolecules. 2018 Aug 24;8(3). pii: biom8030081. doi: 10.3390/biom8030081. PMID:30149595 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also TRNA-guanine transglycosylase 3D structures

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