4puj | pdb_00004puj

tRNA-Guanine Transglycosylase (TGT) in Complex with 6-Amino-2-{[2-(morpholin-4-yl)ethyl]amino}-1H,7H,8H-imidazo[4,5-g]quinazolin-8-one

spinqualitylabelsall models 4puj, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4puj is a 1 chain structure with sequence from Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821. This structure supersedes the now removed PDB entry 3c2n. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.42Å Ligands: CKR, CL, GOL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TGT_ZYMMO Exchanges the guanine residue with 7-aminomethyl-7-deazaguanine in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr). After this exchange, a cyclopentendiol moiety is attached to the 7-aminomethyl group of 7-deazaguanine, resulting in the hypermodified nucleoside queuosine (Q) (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).[HAMAP-Rule:MF_00168] Publication Abstract from PubMed Drug molecules should remain uncharged while traveling through the body and crossing membranes and should only adopt charged state upon protein binding, particularly if charge-assisted interactions can be established in deeply buried binding pockets. Such strategy requires careful pKa design and methods to elucidate whether and where protonation-state changes occur. We investigated the protonation inventory in a series of lin-benzoguanines binding to tRNA-guanine transglycosylase, showing pronounced buffer dependency during ITC measurements. Chemical modifications of the parent scaffold along with ITC measurements, pKa calculations, and site-directed mutagenesis allow elucidating the protonation site. The parent scaffold exhibits two guanidine-type portions, both likely candidates for proton uptake. Even mutually compensating effects resulting from proton release of the protein and simultaneous uptake by the ligand can be excluded. Two adjacent aspartates induce a strong pKa shift at the ligand site, resulting in protonation-state transition. Furthermore, an array of two parallel H-bonds avoiding secondary repulsive effects contributes to the high-affinity binding of the lin-benzoguanines. Chasing Protons: How Isothermal Titration Calorimetry, Mutagenesis, and pKa Calculations Trace the Locus of Charge in Ligand Binding to a tRNA-Binding Enzyme.,Neeb M, Czodrowski P, Heine A, Barandun LJ, Hohn C, Diederich F, Klebe G J Med Chem. 2014 Jul 10;57(13):5554-65. doi: 10.1021/jm500401x. Epub 2014 Jun 23. PMID:24955548 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also TRNA-guanine transglycosylase 3D structures

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