Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA pseudouridine synthase 1, mitochondrial
GI: 70166645
Orf: PP8985
COG: COG0101
UniProt: Q9Y606
Structures: | 4J37 | 4ITS | 4IQM | 4NZ7 | 4NZ6 |
Alpha Fold Predicted Structure: AF-Q9Y606-F1
Enzyme type: pseudouridine synthase
Position of modification - modification: t:28 - Y
t:27 - Y
t:30 - Y
other:236 - Y


PDB Structures:


4J37

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Human pseudouridine (Ψ) synthase Pus1 (hPus1) modifies specific uridine residues in several non-coding RNAs: tRNA, U2 spliceosomal RNA, and steroid receptor activator RNA. We report three structures of the catalytic core domain of hPus1 from two crystal forms, at 1.8Å resolution. The structures are the first of a mammalian Ψ synthase from the set of five Ψ synthase families common to all kingdoms of life. hPus1 adopts a fold similar to bacterial Ψ synthases, with a central antiparallel β-sheet flanked by helices and loops. A flexible hinge at the base of the sheet allows the enzyme to open and close around an electropositive active-site cleft. In one crystal form, a molecule of Mes [2-(N-morpholino)ethane sulfonic acid] mimics the target uridine of an RNA substrate. A positively charged electrostatic surface extends from the active site towards the N-terminus of the catalytic domain, suggesting an extensive binding site specific for target RNAs. Two α-helices C-terminal to the core domain, but unique to hPus1, extend along the back and top of the central β-sheet and form the walls of the RNA binding surface. Docking of tRNA to hPus1 in a productive orientation requires only minor conformational changes to enzyme and tRNA. The docked tRNA is bound by the electropositive surface of the protein employing a completely different binding mode than that seen for the tRNA complex of the Escherichia coli homologue TruA.

Download RCSB-PDB Structures:

Pdb Files   4IQM.pdb   4ITS.pdb   4J37.pdb   4NZ6.pdb   4NZ7.pdb  
Pdbx/mmCIF Files   4IQM.cif   4ITS.cif   4J37.cif   4NZ6.cif   4NZ7.cif  


Protein sequence:

MGLQLRALLGAFGRWTLRLGPRPSCSPRMAGNAEPPPAGAACPQDRRSCSGRAGGDRVWEDGEHPAKKLKSGGDEERREKPPKRKIVLLMAYSGKGYHGMQRNVGSSQFKTIEDDLVSALVRSGCIPENHGEDMRKMSFQRCARTDKGVSAAGQVVSLKVWLIDDILEKINSHLPSHIRILGLKRVTGGFNSKNRCDARTYCYLLPTFAFAHKDRDVQDETYRLSAETLQQVNRLLACYKGTHNFHNFTSQKGPQDPSACRYILEMYCEEPFVREGLEFAVIRVKGQSFMMHQIRKMVGLVVAIVKGYAPESVLERSWGTEKVDVPKAPGLGLVLERVHFEKYNQRFGNDGLHEPLDWAQEEGKVAAFKEEHIYPTIIGTERDERSMAQWLSTLPIHNFSATALTAGGTGAKVPSPLEGSEGDGDTD

Comments:

Specificity of this enzyme was not studied in details. Most probably it is very similar to the specificity of its yest and mouse homologs. Mitochondrial. Exist in two isoforms. Reduced or no activity of Pus1 is related to mitochondrial myopathy and sideroblastic anemia (MLASA). Can modify the Steroid receptor RNA Activator (SRA).




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
U:Y tRNA (t) Lys/∃UU/mitochondrion 27 15772074   
U:Y tRNA (t) Lys/∃UU/mitochondrion 28 15772074   
U:Y tRNA (t) Ile/*AP/eukaryotic cytosol 27 18648068   
U:Y tRNA (t) Ile/*AP/eukaryotic cytosol 30 18648068   
U:Y tRNA (t) Ser/UGA/eukaryotic cytosol 28 22102571   
U:Y other (o) SRA//nucleus 236 24722331   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M G L Q L R A L L G A F G R W T L R L G P R P S C S P R M A G N A E P P P A G A A C P Q D R R S C S G R A G G D R V W E D G E H P A K K L K S G G D E E R R E K P P K R K I V L L M A Y S G K G Y H G M Q R N V G S S Q F K T I E D D L V S A L V R S G C I P E N H G E D M R K M S F Q R C A R T D K G V S A A G Q V V S L K V W L I D D I L E K I N S H L P S H I R I L G L K R V T G G F N S K N R C D A R T Y C Y L L P T F A F A H K D R D V Q D E T Y R L S A E T L Q Q V N R L L A C Y K G T H N F H N F T S Q K G P Q D P S A C R Y I L E M Y C E E P F V R E G L E F A V I R V K G Q S F M M H Q I R K M V G L V V A I V K G Y A P E S V L E R S W G T E K V D V P K A P G L G L V L E R V H F E K Y N Q R F G N D G L H E P L D W A Q E E G K V A A F K E E H I Y P T I I G T E R D E R S M A Q W L S T L P I H N F S A T A L T A G G T G A K V P S P L E G S E G D G D T D

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-Q9Y606-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q9Y606-F1.cif  
DSSP Secondary Structures   Q9Y606.dssp  





Diseases connected to this enzyme:

Description Reaction Disease Name
Mutation in PUS1 gene affects an amino acid, that cause a defect in pseudouridylation. Deficient pseudouridylation of mitochondrial tRNAs has been associated to MLASA U:Y
Mitochondrial myopathy and sideroblastic anemia (MLASA)
LAck of modifications in mitochondrial and cytoplasmic tRNAs from MLASA patients at sites normally modified by Pus1p. U:Y
Mitochondrial myopathy and sideroblastic anemia (MLASA)

Publications:

Title Authors Journal Details PubMed Id DOI
A small RNA derived from RNA coactivator SRA blocks steroid receptor signaling via inhibition of Pus1p-mediated pseudouridylation of SRA: evidence of a novel RNA binding domain in the N-terminus of steroid receptors. Ghosh SK, Patton JR, Spanjaard RA Biochemistry [details] 22998747 -
Pseudouridine synthase 1: a site-specific synthase without strict sequence recognition requirements. Sibert BS, Patton JR Nucleic Acids Res [details] 22102571 -
Partial activity is seen with many substitutions of highly conserved active site residues in human Pseudouridine synthase 1. Sibert BS, Fischel-Ghodsian N, Patton JR RNA [details] 18648068 -
Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. Patton JR, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel-Ghodsian N J Biol Chem [details] 15772074 S0021-9258(20)61767-7
In Human Pseudouridine Synthase 1 (hPus1), a C-Terminal Helical Insert Blocks tRNA from Binding in the Same Orientation as in the Pus1 Bacterial Homologue TruA, Consistent with Their Different Target Selectivities. Czudnochowski N, Wang AL, Finer-Moore J, Stroud RM J Mol Biol [details] 23707380 -
Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model. Huet T, Miannay FA, Patton JR, Thore S... PLoS One [details] 24722331 -

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