5A64

Crystal structure of mouse thiamine triphosphatase in complex with thiamine triphosphate.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.212 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural Determinants for Substrate Binding and Catalysis in Triphosphate Tunnel Metalloenzymes.

Martinez, J.Truffault, V.Hothorn, M.

(2015) J Biol Chem 290: 23348

  • DOI: https://doi.org/10.1074/jbc.M115.674473
  • Primary Citation of Related Structures:  
    5A5Y, 5A60, 5A61, 5A64, 5A65, 5A66, 5A67, 5A68

  • PubMed Abstract: 

    Triphosphate tunnel metalloenzymes (TTMs) are present in all kingdoms of life and catalyze diverse enzymatic reactions such as mRNA capping, the cyclization of adenosine triphosphate, the hydrolysis of thiamine triphosphate, and the synthesis and breakdown of inorganic polyphosphates. TTMs have an unusual tunnel domain fold that harbors substrate- and metal co-factor binding sites. It is presently poorly understood how TTMs specifically sense different triphosphate-containing substrates and how catalysis occurs in the tunnel center. Here we describe substrate-bound structures of inorganic polyphosphatases from Arabidopsis and Escherichia coli, which reveal an unorthodox yet conserved mode of triphosphate and metal co-factor binding. We identify two metal binding sites in these enzymes, with one co-factor involved in substrate coordination and the other in catalysis. Structural comparisons with a substrate- and product-bound mammalian thiamine triphosphatase and with previously reported structures of mRNA capping enzymes, adenylate cyclases, and polyphosphate polymerases suggest that directionality of substrate binding defines TTM catalytic activity. Our work provides insight into the evolution and functional diversification of an ancient enzyme family.


  • Organizational Affiliation

    From the Structural Plant Biology Laboratory, Department of Botany and Plant Biology, University of Geneva, 1211 Geneva, Switzerland and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
THIAMINE TRIPHOSPHATASE
A, B
226Mus musculusMutation(s): 0 
EC: 3.6.1.28
UniProt
Find proteins for Q8JZL3 (Mus musculus)
Explore Q8JZL3 
Go to UniProtKB:  Q8JZL3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8JZL3
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
V4E
Query on V4E

Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]
Thiamine Triphosphate
C12 H20 N4 O10 P3 S
IWLROWZYZPNOFC-UHFFFAOYSA-O
PGE
Query on PGE

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A]
TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.212 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.181α = 90
b = 93.578β = 93.04
c = 70.775γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-08-05
    Type: Initial release
  • Version 1.1: 2015-08-12
    Changes: Database references
  • Version 1.2: 2015-10-07
    Changes: Database references
  • Version 1.3: 2017-09-27
    Changes: Data collection
  • Version 1.4: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description