Journal:MicroPubl Biol:000570
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- | - | + | <StructureSection load='' size='450' side='right' scene='91/913474/Cv/5' caption=''> |
+ | ===Biochemical and structural characterization of the flavodoxin-like domain of the ''Schizosaccharomyces japonicus'' putative tRNAPhe 4-demethylwyosine synthase TYW1 in complex with FMN=== | ||
+ | <big>Ljiljana Sjekloća, Adrian R. Ferré-D’Amaré</big> <ref>doi: 10.17912/micropub.biology.000570</ref> | ||
+ | <hr/> | ||
+ | <b>Molecular Tour</b><br> | ||
+ | Amidst intriguing complexity of tRNA non canonical bases, wyosine stands out for being the only fluorescent nucleobase. Sequential enzymatic reactions transform specifically phenylalanine tRNA G37 in a tricyclic, highly hydrophobic, hypermodified nucleoside adjacent to the anticodon loop where it may influence anticodon flexibility and translation efficiency. | ||
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+ | S-adenosyl-L-methionine-dependent 4-demethylwyosin synthase TYW1 is an iron-sulfur enzyme which merges pyruvate with pyrimidine-imidazole ring of methylated G37 to generate 4-demethylwyosine imG-14, the first tricyclic intermediate in wyosine biosynthesis. In Eukaryotes TYW1 is a two-domain protein which contains a flavodoxin-like domain at its amino-terminus and an iron-sulfur cluster carboxyl-terminal domain. We solved the crystal structure of fungal Tyw1 flavodoxin-like domain in complex with FMN (PDB [[6pup]] and [[6puq]]). | ||
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+ | The crystallographic model (PDB [[6pup]]) contains two Mn (II) ions: | ||
+ | *<scene name='91/913474/Cv/6'>1st view</scene>. | ||
+ | *<scene name='91/913474/Cv/9'>2nd view. Rotated ~ 90° clockwise around the vertical axis, respective to the orientation shown at 1st view</scene>. | ||
+ | *<scene name='91/913474/Cv/8'>3rd view. Rotated ~ 90° clockwise around the horizontal axis, respective to the orientation shown at 1st view</scene>. | ||
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+ | The crystallographic model (PDB [[6pup]]), electrostatic potential: | ||
+ | *<scene name='91/913474/Cv/10'>1st view</scene>. | ||
+ | *<scene name='91/913474/Cv/11'>2nd view. Rotated ~ 90° clockwise around the vertical axis, respective to the orientation shown at 1st view</scene>. | ||
+ | *<scene name='91/913474/Cv/12'>3rd view. Rotated ~ 90° clockwise around the horizontal axis, respective to the orientation shown at 1st view</scene>. | ||
+ | |||
+ | The crystallographic model (PDB [[6pup]]) contains two Mn (II) ions bridged by a water molecule (salmon and red spheres, respectively). | ||
+ | *<scene name='91/913474/Cv/14'>1st view</scene>. | ||
+ | *<scene name='91/913474/Cv/15'>2nd view after ~180° rotation around the vertical axis</scene>. | ||
+ | |||
+ | <span class="bg-yellow"><span class="far fa-hand-point-right"></span> Remember to drag the structures with the mouse to rotate them.</span> | ||
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+ | <scene name='91/913474/Cv/21'>FMN binding site</scene>. FMN is in yellow ball-and-stick representation. The residues contacting FMN, hydrogen bonds (white dashed lines), and selected water molecules (red spheres) are shown. The TYW1 residues are in pink. | ||
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+ | Diametrically opposite the FMN binding site there is a system of several loops, the <scene name='91/913474/Cv/24'>longest of which (residues 168-180)</scene> contains <scene name='91/913474/Cv/26'>Asp168-Phe169-Arg170 and Leu176</scene>, residues conserved in all TYW1 proteins. <scene name='91/913474/Cv/23'>Superposition according to DALI search</scene>. This loop is the most structurally dissimilar from the nearest structural homologues identified by a DALI search: eukaryotic NADP(H)-cytochrome 450 diflavin oxidoreductase ([[3qfc]]) and nitric-oxide synthase ([[1tll]]), and bacterial flavodoxin ([[5lji]]) and sulfite reductase NADP(H) flavoprotein ([[1ykg]]). The [http://ekhidna2.biocenter.helsinki.fi/dali/ DALI server] was used. | ||
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+ | TYW1 structural similarity to enzymes which couple FAD/FMN and NADP(H) coenzymes for their activity, together with the presence of an unexpected metal binding site, point to a very complex regulation of TYW1 by cell energy metabolism. | ||
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+ | '''PDB references:''' 1.9 A crystal structure of flavodoxin-like domain of ''Schizosaccharomyces japonicus'' putative tRNAPhe 4-demethylwyosine synthase TYW1 in complex with FMN [[6pup]]; 1.56 A crystal structure of flavodoxin-like domain of ''Schizosaccharomyces japonicus'' putative tRNAPhe 4-demethylwyosine synthase TYW1 in complex with FMN [[6puq]]. | ||
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+ | <b>References</b><br> | ||
+ | <references/> | ||
+ | </StructureSection> | ||
+ | __NOEDITSECTION__ |
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