2V57

Crystal structure of the TetR-like transcriptional regulator LfrR from Mycobacterium smegmatis in complex with proflavine

PDB DOI: https://doi.org/10.2210/pdb2V57/pdb

Classification: TRANSCRIPTION
Organism(s): Mycolicibacterium smegmatis
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2008-10-02 Released: 2009-10-20
Deposition Author(s): Bellinzoni, M., Buroni, S., Riccardi, G., De Rossi, E., Alzari, P.M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 ?
R-Value Free: 0.234
R-Value Work: 0.196
R-Value Observed: 0.198

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Structural Plasticity and Distinct Drug-Binding Modes of Lfrr, a Mycobacterial Efflux Pump Regulator.

Bellinzoni, M., Buroni, S., Schaeffer, F., Riccardi, G., De Rossi, E., Alzari, P.M.

(2009) J Bacteriol 191: 7531

PubMed: 19820093 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1128/JB.00631-09
Primary Citation of Related Structures:
2V57, 2WGB

PubMed Abstract:
The TetR-like transcriptional repressor LfrR controls the expression of the gene encoding the Mycobacterium smegmatis efflux pump LfrA, which actively extrudes fluoroquinolones, cationic dyes, and anthracyclines from the cell and promotes intrinsic antibiotic resistance. The crystal structure of the apoprotein form of the repressor reveals a structurally asymmetric homodimer exhibiting local unfolding and a blocked drug-binding site, emphasizing the significant conformational plasticity of the protein necessary for DNA and multidrug recognition. Crystallographic and calorimetric studies of LfrR-drug complexes further confirm the intrinsic flexibility of the homodimer, which provides a dynamic mechanism to broaden multidrug binding specificity and may be a general property of transcriptional repressors regulating microbial efflux pump expression.

Organizational Affiliation

Institut Pasteur, Unité de Biochimie Structurale and CNRS URA 2185, Institut Pasteur, 75724 Paris Cedex 15, France.

Macromolecule Content

Total Structure Weight: 83.91 kDa
Atom Count: 5,758
Modelled Residue Count: 695
Deposited Residue Count: 760
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
TETR FAMILY TRANSCRIPTIONAL REPRESSOR LFRR	A, B, C, D	190	Mycolicibacterium smegmatis	Mutation(s): 0
UniProt
Find proteins for Q58L87 (Mycolicibacterium smegmatis) Explore Q58L87 Go to UniProtKB: Q58L87
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q58L87
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
PRL Query on PRL Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth C] MOL2 format, chain E [auth A] MOL2 format, chain I [auth C] mmCIF format, chain E [auth A] mmCIF format, chain I [auth C]	E [auth A], I [auth C]	PROFLAVIN C₁₃ H₁₁ N₃ WDVSHHCDHLJJJR-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain I [auth C] Interactions & Density Focus chain E [auth A] Focus chain I [auth C]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain J [auth C] SDF format, chain L [auth D] SDF format, chain M [auth D] SDF format, chain N [auth D] SDF format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D] MOL2 format, chain M [auth D] MOL2 format, chain N [auth D] MOL2 format, chain G [auth B] mmCIF format, chain H [auth B] mmCIF format, chain J [auth C] mmCIF format, chain L [auth D] mmCIF format, chain M [auth D] mmCIF format, chain N [auth D] mmCIF format, chain G [auth B]	G [auth B] H [auth B] J [auth C] L [auth D] M [auth D] G [auth B], H [auth B], J [auth C], L [auth D], M [auth D], N [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain G [auth B] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D] Focus chain M [auth D] Focus chain N [auth D] Interactions & Density Focus chain G [auth B] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D] Focus chain M [auth D] Focus chain N [auth D]
IPA Query on IPA Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain K [auth C] MOL2 format, chain F [auth A] MOL2 format, chain K [auth C] mmCIF format, chain F [auth A] mmCIF format, chain K [auth C]	F [auth A], K [auth C]	ISOPROPYL ALCOHOL C₃ H₈ O KFZMGEQAYNKOFK-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain K [auth C] Interactions & Density Focus chain F [auth A] Focus chain K [auth C]

Binding Affinity Annotations
ID	Source	Binding Affinity
PRL	PDBBind: 2V57	Kd: 79 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.90 ?
R-Value Free: 0.234
R-Value Work: 0.196
R-Value Observed: 0.198
Space Group: P 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 48.3	α = 63.88
b = 62.44	β = 88.34
c = 70.64	γ = 88.13

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
SCALA	data scaling
MOLREP	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-10-20

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2009-10-20
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other