4J37

Crystal structure of the catalytic domain of human Pus1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

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, A.L.Finer-Moore, J.Stroud, R.M.

(2013) J Mol Biol 425: 3875-3887

  • DOI: https://doi.org/10.1016/j.jmb.2013.05.014
  • Primary Citation of Related Structures:  
    4IQM, 4ITS, 4J37

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
tRNA pseudouridine synthase A, mitochondrial336Homo sapiensMutation(s): 0 
Gene Names: PUS1PP8985
EC: 5.4.99.12
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y606 (Homo sapiens)
Explore Q9Y606 
Go to UniProtKB:  Q9Y606
PHAROS:  Q9Y606
GTEx:  ENSG00000177192 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y606
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.95α = 90
b = 51.95β = 90
c = 445.49γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
PHASERphasing
ELVESrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-06-05
    Type: Initial release
  • Version 1.1: 2013-10-23
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2019-07-17
    Changes: Data collection, Refinement description
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description