5JMN

Fusidic acid bound AcrB

PDB DOI: https://doi.org/10.2210/pdb5JMN/pdb

Classification: TRANSPORT PROTEIN
Organism(s): Escherichia coli K-12, synthetic construct
Expression System: Escherichia coli BL21(DE3), Escherichia coli
Mutation(s): No
Membrane Protein: Yes PDBTMMemProtMDmpstruc

Deposited: 2016-04-29 Released: 2016-12-21
Deposition Author(s): Oswald, C., Tam, H.K., Pos, K.M.
Funding Organization(s): German Research Foundation

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 ?
R-Value Free: 0.261
R-Value Work: 0.225
R-Value Observed: 0.227

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

Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB.

Oswald, C., Tam, H.K., Pos, K.M.

(2016) Nat Commun 7: 13819-13819

PubMed: 27982032 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/ncomms13819
Primary Citation of Related Structures:
5JMN

PubMed Abstract:
The deployment of multidrug efflux pumps is a powerful defence mechanism for Gram-negative bacterial cells when exposed to antimicrobial agents. The major multidrug efflux transport system in Escherichia coli, AcrAB-TolC, is a tripartite system using the proton-motive force as an energy source. The polyspecific substrate-binding module AcrB uses various pathways to sequester drugs from the periplasm and outer leaflet of the inner membrane. Here we report the asymmetric AcrB structure in complex with fusidic acid at a resolution of 2.5?? and mutational analysis of the putative fusidic acid binding site at the transmembrane domain. A groove shaped by the interface between transmembrane helix 1 (TM1) and TM2 specifically binds fusidic acid and other lipophilic carboxylated drugs. We propose that these bound drugs are actively displaced by an upward movement of TM2 towards the AcrB periplasmic porter domain in response to protonation events in the transmembrane domain.

Organizational Affiliation

Institute of Biochemistry, Goethe University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.

Macromolecule Content

Total Structure Weight: 393.61 kDa
Atom Count: 27,640
Modelled Residue Count: 3,413
Deposited Residue Count: 3,509
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Multidrug efflux pump subunit AcrB	A, B, C	1,057	Escherichia coli K-12	Mutation(s): 0 Gene Names: acrB, acrE, b0462, JW0451 Membrane Entity: Yes
UniProt
Find proteins for P31224 (Escherichia coli (strain K12)) Explore P31224 Go to UniProtKB: P31224
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P31224
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
DARPin	D, E	169	synthetic construct	Mutation(s): 0 Gene Names: Artificial gene
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 11 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
PTY Query on PTY Download Ideal Coordinates CCD File SDF format, chain IA [auth C] SDF format, chain JA [auth C] SDF format, chain U [auth B] SDF format, chain KA [auth C] MOL2 format, chain IA [auth C] MOL2 format, chain JA [auth C] MOL2 format, chain U [auth B] MOL2 format, chain KA [auth C] mmCIF format, chain IA [auth C] mmCIF format, chain JA [auth C] mmCIF format, chain U [auth B] mmCIF format, chain KA [auth C]	IA [auth C], JA [auth C], KA [auth C], U [auth B]	PHOSPHATIDYLETHANOLAMINE C₄₀ H₈₀ N O₈ P NJGIRBISCGPRPF-KXQOOQHDSA-N		Interactions Focus chain IA [auth C] Focus chain JA [auth C] Focus chain KA [auth C] Focus chain U [auth B] Interactions & Density Focus chain IA [auth C] Focus chain JA [auth C] Focus chain KA [auth C] Focus chain U [auth B]
FUA Query on FUA Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain F [auth A] SDF format, chain O [auth B] MOL2 format, chain AA [auth C] MOL2 format, chain F [auth A] MOL2 format, chain O [auth B] mmCIF format, chain AA [auth C] mmCIF format, chain F [auth A] mmCIF format, chain O [auth B]	AA [auth C], F [auth A], O [auth B]	FUSIDIC ACID C₃₁ H₄₈ O₆ IECPWNUMDGFDKC-MZJAQBGESA-N		Interactions Focus chain AA [auth C] Focus chain F [auth A] Focus chain O [auth B] Interactions & Density Focus chain AA [auth C] Focus chain F [auth A] Focus chain O [auth B]
LMT Query on LMT Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain I [auth A] SDF format, chain P [auth B] SDF format, chain R [auth B] SDF format, chain BA [auth C] SDF format, chain CA [auth C] SDF format, chain DA [auth C] SDF format, chain EA [auth C] SDF format, chain H [auth A] SDF format, chain Q [auth B] MOL2 format, chain G [auth A] MOL2 format, chain I [auth A] MOL2 format, chain P [auth B] MOL2 format, chain R [auth B] MOL2 format, chain BA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain DA [auth C] MOL2 format, chain EA [auth C] MOL2 format, chain H [auth A] MOL2 format, chain Q [auth B] mmCIF format, chain G [auth A] mmCIF format, chain I [auth A] mmCIF format, chain P [auth B] mmCIF format, chain R [auth B] mmCIF format, chain BA [auth C] mmCIF format, chain CA [auth C] mmCIF format, chain DA [auth C] mmCIF format, chain EA [auth C] mmCIF format, chain H [auth A] mmCIF format, chain Q [auth B]	BA [auth C] CA [auth C] DA [auth C] EA [auth C] G [auth A] BA [auth C], CA [auth C], DA [auth C], EA [auth C], G [auth A], H [auth A], I [auth A], P [auth B], Q [auth B], R [auth B]	DODECYL-BETA-D-MALTOSIDE C₂₄ H₄₆ O₁₁ NLEBIOOXCVAHBD-QKMCSOCLSA-N		Interactions Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain EA [auth C] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Interactions & Density Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain EA [auth C] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B]
P3G Query on P3G Download Ideal Coordinates CCD File SDF format, chain X [auth B] MOL2 format, chain X [auth B] mmCIF format, chain X [auth B]	X [auth B]	3,6,9,12,15-PENTAOXAHEPTADECANE C₁₂ H₂₆ O₅ HYDWALOBQJFOMS-UHFFFAOYSA-N		Interactions Focus chain X [auth B] Interactions & Density Focus chain X [auth B]
ETE Query on ETE Download Ideal Coordinates CCD File SDF format, chain M [auth A] SDF format, chain OA [auth C] SDF format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain OA [auth C] MOL2 format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain OA [auth C] mmCIF format, chain L [auth A]	L [auth A], M [auth A], OA [auth C]	2-{2-[2-2-(METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL C₉ H₂₀ O₅ ZNYRFEPBTVGZDN-UHFFFAOYSA-N		Interactions Focus chain L [auth A] Focus chain M [auth A] Focus chain OA [auth C] Interactions & Density Focus chain L [auth A] Focus chain M [auth A] Focus chain OA [auth C]
D12 Query on D12 Download Ideal Coordinates CCD File SDF format, chain NA [auth C] SDF format, chain LA [auth C] SDF format, chain MA [auth C] SDF format, chain V [auth B] MOL2 format, chain NA [auth C] MOL2 format, chain LA [auth C] MOL2 format, chain MA [auth C] MOL2 format, chain V [auth B] mmCIF format, chain NA [auth C] mmCIF format, chain LA [auth C] mmCIF format, chain MA [auth C] mmCIF format, chain V [auth B]	LA [auth C], MA [auth C], NA [auth C], V [auth B]	DODECANE C₁₂ H₂₆ SNRUBQQJIBEYMU-UHFFFAOYSA-N		Interactions Focus chain LA [auth C] Focus chain MA [auth C] Focus chain NA [auth C] Focus chain V [auth B] Interactions & Density Focus chain LA [auth C] Focus chain MA [auth C] Focus chain NA [auth C] Focus chain V [auth B]
D10 Query on D10 Download Ideal Coordinates CCD File SDF format, chain Y [auth B] SDF format, chain Z [auth B] MOL2 format, chain Y [auth B] MOL2 format, chain Z [auth B] mmCIF format, chain Y [auth B] mmCIF format, chain Z [auth B]	Y [auth B], Z [auth B]	DECANE C₁₀ H₂₂ DIOQZVSQGTUSAI-UHFFFAOYSA-N		Interactions Focus chain Y [auth B] Focus chain Z [auth B] Interactions & Density Focus chain Y [auth B] Focus chain Z [auth B]
OCT Query on OCT Download Ideal Coordinates CCD File SDF format, chain PA [auth C] SDF format, chain W [auth B] MOL2 format, chain PA [auth C] MOL2 format, chain W [auth B] mmCIF format, chain PA [auth C] mmCIF format, chain W [auth B]	PA [auth C], W [auth B]	N-OCTANE C₈ H₁₈ TVMXDCGIABBOFY-UHFFFAOYSA-N		Interactions Focus chain PA [auth C] Focus chain W [auth B] Interactions & Density Focus chain PA [auth C] Focus chain W [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain FA [auth C] MOL2 format, chain J [auth A] MOL2 format, chain FA [auth C] mmCIF format, chain J [auth A] mmCIF format, chain FA [auth C]	FA [auth C], J [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain FA [auth C] Focus chain J [auth A] Interactions & Density Focus chain FA [auth C] Focus chain J [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain GA [auth C] SDF format, chain RA [auth D] SDF format, chain TA [auth E] SDF format, chain HA [auth C] SDF format, chain K [auth A] SDF format, chain S [auth B] SDF format, chain SA [auth E] SDF format, chain T [auth B] MOL2 format, chain GA [auth C] MOL2 format, chain RA [auth D] MOL2 format, chain TA [auth E] MOL2 format, chain HA [auth C] MOL2 format, chain K [auth A] MOL2 format, chain S [auth B] MOL2 format, chain SA [auth E] MOL2 format, chain T [auth B] mmCIF format, chain GA [auth C] mmCIF format, chain RA [auth D] mmCIF format, chain TA [auth E] mmCIF format, chain HA [auth C] mmCIF format, chain K [auth A] mmCIF format, chain S [auth B] mmCIF format, chain SA [auth E] mmCIF format, chain T [auth B]	GA [auth C] HA [auth C] K [auth A] RA [auth D] S [auth B] GA [auth C], HA [auth C], K [auth A], RA [auth D], S [auth B], SA [auth E], T [auth B], TA [auth E]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain GA [auth C] Focus chain HA [auth C] Focus chain K [auth A] Focus chain RA [auth D] Focus chain S [auth B] Focus chain SA [auth E] Focus chain T [auth B] Focus chain TA [auth E] Interactions & Density Focus chain GA [auth C] Focus chain HA [auth C] Focus chain K [auth A] Focus chain RA [auth D] Focus chain S [auth B] Focus chain SA [auth E] Focus chain T [auth B] Focus chain TA [auth E]
HEX Query on HEX Download Ideal Coordinates CCD File SDF format, chain QA [auth C] SDF format, chain N [auth A] MOL2 format, chain QA [auth C] MOL2 format, chain N [auth A] mmCIF format, chain QA [auth C] mmCIF format, chain N [auth A]	N [auth A], QA [auth C]	HEXANE C₆ H₁₄ VLKZOEOYAKHREP-UHFFFAOYSA-N		Interactions Focus chain N [auth A] Focus chain QA [auth C] Interactions & Density Focus chain N [auth A] Focus chain QA [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.50 ?
R-Value Free: 0.261
R-Value Work: 0.225
R-Value Observed: 0.227
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( ? )	Angle ( ? )
a = 145.654	α = 90
b = 163.248	β = 90
c = 246.042	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XDS	data scaling
REFMAC	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2016-12-21

Deposition Author(s):

Oswald, C.

Tam, H.K.

Pos, K.M.

Funding Organization	Location	Grant Number
German Research Foundation	Germany	SFB807 (Transport and Communication across Biological Membranes
German Research Foundation	Germany	DFG EXC115 (Cluster of Excellence Frankfurt Macromolecular Complexes)

Revision History (Full details and data files)

Version 1.0: 2016-12-21
Type: Initial release
Version 1.1: 2016-12-28
Changes: Database references
Version 1.2: 2017-01-11
Changes: Database references
Version 1.3: 2024-01-10
Changes: Data collection, Database references, Refinement description