4RPH

Crystal structure of Micobacterium tuberculosis UDP-Galactopyranose mutase in complex with substrate UDP-Galp (reduced)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural Basis of Ligand Binding to UDP-Galactopyranose Mutase from Mycobacterium tuberculosis Using Substrate and Tetrafluorinated Substrate Analogues.

van Straaten, K.E.Kuttiyatveetil, J.R.Sevrain, C.M.Villaume, S.A.Jimenez-Barbero, J.Linclau, B.Vincent, S.P.Sanders, D.A.

(2015) J Am Chem Soc 137: 1230-1244

  • DOI: https://doi.org/10.1021/ja511204p
  • Primary Citation of Related Structures:  
    4RPG, 4RPH, 4RPJ, 4RPK, 4RPL

  • PubMed Abstract: 

    UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized flavin and reduced flavin). In addition, we have determined the complex structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated analogues of both UDP-Galp (UDP-F4-Galp) and UDP-Galf (UDP-F4-Galf)), which represent the first complex structures of UGM with an analogue in the furanose form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues bound to a protein. These structures provide detailed insight into ligand recognition by MtUGM and show an overall binding mode similar to those reported for other prokaryotic UGMs. The binding of the ligand induces conformational changes in the enzyme, allowing ligand binding and active-site closure. In addition, the complex structure of MtUGM with UDP-F4-Galf reveals the first detailed insight into how the furanose moiety binds to UGM. In particular, this study confirmed that the furanoside adopts a high-energy conformation ((4)E) within the catalytic pocket. Moreover, these investigations provide structural insights into the enhanced binding of the dideoxy-tetrafluorinated sugars compared to unmodified analogues. These results will help in the design of carbohydrate mimetics and drug development, and show the enormous possibilities for the use of polyfluorination in the design of carbohydrate mimetics.


  • Organizational Affiliation

    Department of Chemistry, University of Saskatchewan , 110 Science Place, Saskatoon S7N 5C9, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UDP-galactopyranose mutaseA [auth B],
B [auth A],
C
399Mycobacterium tuberculosis H37RvMutation(s): 1 
Gene Names: glfglfARv3809c
EC: 5.4.99.9
UniProt
Find proteins for P9WIQ1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WIQ1 
Go to UniProtKB:  P9WIQ1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WIQ1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 171.73α = 90
b = 99.47β = 110.17
c = 100.24γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
MOLREPphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
MxDCdata collection
AutoProcessdata reduction
AutoProcessdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-01-21
    Type: Initial release
  • Version 1.1: 2015-02-04
    Changes: Database references
  • Version 1.2: 2015-02-11
    Changes: Database references
  • Version 1.3: 2017-11-22
    Changes: Database references, Refinement description
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description