5LZI

Porcine heat-labile enterotoxin R13H in complex with inhibitor MM146


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.176 
  • R-Value Work: 0.147 
  • R-Value Observed: 0.148 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Towards new cholera prophylactics and treatment: Crystal structures of bacterial enterotoxins in complex with GM1 mimics.

Heggelund, J.E.Mackenzie, A.Martinsen, T.Benjamin Heim, J.Cheshev, P.Bernardi, A.Krengel, U.

(2017) Sci Rep 7: 2326-2326

  • DOI: https://doi.org/10.1038/s41598-017-02179-0
  • Primary Citation of Related Structures:  
    5LZG, 5LZH, 5LZI, 5LZJ

  • PubMed Abstract: 

    Cholera is a life-threatening disease in many countries, and new drugs are clearly needed. C-glycosidic antagonists may serve such a purpose. Here we report atomic-resolution crystal structures of three such compounds in complexes with the cholera toxin. The structures give unprecedented atomic details of the molecular interactions and show how the inhibitors efficiently block the GM1 binding site. These molecules are well suited for development into low-cost prophylactic drugs, due to their relatively easy synthesis and their resistance to glycolytic enzymes. One of the compounds links two toxin B-pentamers in the crystal structure, which may yield improved inhibition through the formation of toxin aggregates. These structures can spark the improved design of GM1 mimics, either alone or as multivalent inhibitors connecting multiple GM1-binding sites. Future developments may further include compounds that link the primary and secondary binding sites. Serving as decoys, receptor mimics may lessen symptoms while avoiding the use of antibiotics.


  • Organizational Affiliation

    Department of Chemistry, University of Oslo, P.O. Box 1033, NO-0315, Blindern, Norway. j.e.heggelund@farmasi.uio.no.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat-labile enterotoxin B chain
A, B, C, D, E
103Escherichia coliMutation(s): 1 
Gene Names: eltBltpB
UniProt
Find proteins for P32890 (Escherichia coli)
Explore P32890 
Go to UniProtKB:  P32890
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP32890
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7DB
Query on 7DB

Download Ideal Coordinates CCD File 
K [auth B],
M [auth C],
P [auth D],
Q [auth E]
(2~{R},4~{S},5~{R},6~{R})-5-acetamido-2-[4-[(2~{S})-3-[2-[(2~{S},3~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]ethylamino]-3-oxidanylidene-2-(2-phenylethanoylamino)propyl]-1,2,3-triazol-1-yl]-4-oxidanyl-6-[(1~{R},2~{R})-1,2,3-tris(oxidanyl)propyl]oxane-2-carboxylic acid
C32 H46 N6 O15
VJJPXKHAIAQVCK-WZAWTCGUSA-N
7BQ
Query on 7BQ

Download Ideal Coordinates CCD File 
G [auth A](2~{R},4~{S},5~{R},6~{R})-5-acetamido-2-[4-[(2~{R})-3-[2-[(2~{S},3~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]ethylamino]-3-oxidanylidene-2-(2-phenylethanoylamino)propyl]-1,2,3-triazol-1-yl]-4-oxidanyl-6-[(1~{R},2~{R})-1,2,3-tris(oxidanyl)propyl]oxane-2-carboxylic acid
C32 H46 N6 O15
VJJPXKHAIAQVCK-WOQXIOLNSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
H [auth A]DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
N [auth C]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
J [auth B],
L [auth C],
O [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.176 
  • R-Value Work: 0.147 
  • R-Value Observed: 0.148 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.17α = 90
b = 75.87β = 90
c = 125.18γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-31
    Type: Initial release
  • Version 1.1: 2017-06-07
    Changes: Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description