6ZOB

3-Formylrifamycin SV binding to the access pocket of AcrB L protomer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.239 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Allosteric drug transport mechanism of multidrug transporter AcrB.

Tam, H.K.Foong, W.E.Oswald, C.Herrmann, A.Zeng, H.Pos, K.M.

(2021) Nat Commun 12: 3889-3889

  • DOI: https://doi.org/10.1038/s41467-021-24151-3
  • Primary Citation of Related Structures:  
    6ZO5, 6ZO6, 6ZO7, 6ZO8, 6ZO9, 6ZOA, 6ZOB, 6ZOC, 6ZOD, 6ZOE, 6ZOF, 6ZOG, 6ZOH

  • PubMed Abstract: 

    Gram-negative bacteria maintain an intrinsic resistance mechanism against entry of noxious compounds by utilizing highly efficient efflux pumps. The E. coli AcrAB-TolC drug efflux pump contains the inner membrane H + /drug antiporter AcrB comprising three functionally interdependent protomers, cycling consecutively through the loose (L), tight (T) and open (O) state during cooperative catalysis. Here, we present 13 X-ray structures of AcrB in intermediate states of the transport cycle. Structure-based mutational analysis combined with drug susceptibility assays indicate that drugs are guided through dedicated transport channels toward the drug binding pockets. A co-structure obtained in the combined presence of erythromycin, linezolid, oxacillin and fusidic acid shows binding of fusidic acid deeply inside the T protomer transmembrane domain. Thiol cross-link substrate protection assays indicate that this transmembrane domain-binding site can also accommodate oxacillin or novobiocin but not erythromycin or linezolid. AcrB-mediated drug transport is suggested to be allosterically modulated in presence of multiple drugs.


  • Organizational Affiliation

    Institute of Biochemistry, Goethe-University Frankfurt, Frankfurt am Main, Germany. [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Multidrug efflux pump subunit AcrB
A, B, C
1,057Escherichia coli K-12Mutation(s): 0 
Gene Names: acrBacrEb0462JW0451
Membrane Entity: Yes 
UniProt
Find proteins for P31224 (Escherichia coli (strain K12))
Explore P31224 
Go to UniProtKB:  P31224
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP31224
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DARPIN
D, E
169synthetic constructMutation(s): 0 
Gene Names: ARTIFICIAL GENE
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 11 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3YI (Subject of Investigation/LOI)
Query on 3YI

Download Ideal Coordinates CCD File 
M [auth A](2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-8-formyl-5,6,9,17,19-pentahydroxy-23-methoxy-2,4,12,16,18,20,22-heptam ethyl-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca[1,11,13]trienoimino)naphtho[2,1-b]furan-21-yl acetate
C38 H47 N O13
BBNQHOMJRFAQBN-UPZFVJMDSA-N
LMT
Query on LMT

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F [auth A]
G [auth A]
H [auth A]
K [auth A]
O [auth B]
F [auth A],
G [auth A],
H [auth A],
K [auth A],
O [auth B],
T [auth C]
DODECYL-BETA-D-MALTOSIDE
C24 H46 O11
NLEBIOOXCVAHBD-QKMCSOCLSA-N
DDR
Query on DDR

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P [auth B](2S)-3-hydroxypropane-1,2-diyl didecanoate
C23 H44 O5
GNSDEDOVXZDMKM-NRFANRHFSA-N
ETE
Query on ETE

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L [auth A]2-{2-[2-2-(METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL
C9 H20 O5
ZNYRFEPBTVGZDN-UHFFFAOYSA-N
DDQ
Query on DDQ

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Q [auth B]DECYLAMINE-N,N-DIMETHYL-N-OXIDE
C12 H27 N O
ZRKZFNZPJKEWPC-UHFFFAOYSA-N
D10
Query on D10

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U [auth C]DECANE
C10 H22
DIOQZVSQGTUSAI-UHFFFAOYSA-N
OCT
Query on OCT

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R [auth B]N-OCTANE
C8 H18
TVMXDCGIABBOFY-UHFFFAOYSA-N
GOL
Query on GOL

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J [auth A],
S [auth B],
V [auth C],
X [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
HEX
Query on HEX

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I [auth A]HEXANE
C6 H14
VLKZOEOYAKHREP-UHFFFAOYSA-N
EDO
Query on EDO

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N [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CL
Query on CL

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W [auth C]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.239 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 145.361α = 90
b = 160.195β = 90
c = 244.341γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
MOLREPphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research Foundation (DFG)GermanyDFG-EXC115
German-Israeli Foundation for Research and DevelopmentGermanyI-1202-248.9/2012
European Communitys Seventh Framework ProgrammeEuropean UnionFP7/2007-2013

Revision History  (Full details and data files)

  • Version 1.0: 2021-05-19
    Type: Initial release
  • Version 1.1: 2021-07-07
    Changes: Database references
  • Version 1.2: 2021-07-14
    Changes: Database references
  • Version 1.3: 2024-01-31
    Changes: Data collection, Database references, Refinement description