4H67

Crystal structure of HMP synthase Thi5 from S. cerevisiae


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

The Last Piece in the Vitamin B1 Biosynthesis Puzzle: STRUCTURAL AND FUNCTIONAL INSIGHT INTO YEAST 4-AMINO-5-HYDROXYMETHYL-2-METHYLPYRIMIDINE PHOSPHATE (HMP-P) SYNTHASE.

Coquille, S.Roux, C.Fitzpatrick, T.B.Thore, S.

(2012) J Biol Chem 287: 42333-42343

  • DOI: https://doi.org/10.1074/jbc.M112.397240
  • Primary Citation of Related Structures:  
    4H65, 4H67, 4H6D

  • PubMed Abstract: 

    Vitamin B(1) is essential for all organisms being well recognized as a necessary cofactor for key metabolic pathways such as glycolysis, and was more recently implicated in DNA damage responses. Little is known about the enzyme responsible for the formation of the pyrimidine moiety (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase). We report a structure-function study of the HMP-P synthase from yeast, THI5p. Our crystallographic structure shows that THI5p is a mix between periplasmic binding proteins and pyridoxal 5'-phosphate-dependent enzymes. Mutational and yeast complementation studies identify the key residues for HMP-P biosynthesis as well as the use of pyridoxal 5'-phosphate as a substrate rather than as a cofactor. Furthermore, we could show that iron binding to HMP-P synthase is essential for the reaction.


  • Organizational Affiliation

    Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Pyrimidine precursor biosynthesis enzyme THI5
A, B, C, D, E
A, B, C, D, E, F, G, H
346Saccharomyces cerevisiaeMutation(s): 3 
Gene Names: THI5YFL058W
UniProt
Find proteins for P43534 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore P43534 
Go to UniProtKB:  P43534
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP43534
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLP
Query on PLP

Download Ideal Coordinates CCD File 
L [auth B]PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
I [auth A]
J [auth A]
K [auth A]
M [auth C]
N [auth C]
I [auth A],
J [auth A],
K [auth A],
M [auth C],
N [auth C],
O [auth C],
P [auth C],
Q [auth C],
R [auth C],
S [auth D],
T [auth D],
U [auth D],
V [auth E],
W [auth F],
X [auth G],
Y [auth G],
Z [auth H]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.79α = 90
b = 188.46β = 112.51
c = 101.67γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
CCP4model building
PHENIXrefinement
XDSdata reduction
XDSdata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-17
    Type: Initial release
  • Version 1.1: 2012-10-24
    Changes: Database references, Refinement description, Structure summary
  • Version 1.2: 2013-01-23
    Changes: Database references
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description