2Y6Q

Structure of the TetX monooxygenase in complex with the substrate 7- Iodtetracycline

PDB DOI: https://doi.org/10.2210/pdb2Y6Q/pdb

Classification: OXIDOREDUCTASE
Organism(s): Bacteroides thetaiotaomicron
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2011-01-25 Released: 2011-03-23
Deposition Author(s): Volkers, G., Palm, G.J., Weiss, M.S., Wright, G.D., Hinrichs, W.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.37 ?
R-Value Free: 0.238
R-Value Work: 0.218
R-Value Observed: 0.219

Starting Model: experimental
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Literature

Structural Basis for a New Tetracycline Resistance Mechanism Relying on the Tetx Monooxygenase.

Volkers, G., Palm, G.J., Weiss, M.S., Wright, G.D., Hinrichs, W.

(2011) FEBS Lett 585: 1061

PubMed: 21402075 Search on PubMed
DOI: https://doi.org/10.1016/j.febslet.2011.03.012
Primary Citation of Related Structures:
2XDO, 2XYO, 2Y6Q, 2Y6R

PubMed Abstract:
The flavin-dependent monooxygenase TetX confers resistance to all clinically relevant tetracyclines, including the recently approved, broad-spectrum antibiotic tigecycline (Tygacil?) which is a critical last-ditch defense against multidrug-resistant pathogens. TetX represents the first resistance mechanism against tigecycline, which circumvents both the tet-gene encoded resistances, relying on active efflux of tetracyclines, and ribosomal protection proteins. The alternative enzyme-based mechanism of TetX depends on regioselective hydroxylation of tetracycline antibiotics to 11a-hydroxy-tetracyclines. Here, we report the X-ray crystallographic structure determinations at 2.1? resolution of native TetX from Bacteroides thetaiotaomicron and its complexes with tetracyclines. Our crystal structures explain the extremely versatile substrate diversity of the enzyme and provide a first step towards the rational design of novel tetracycline derivatives to counter TetX-based resistance prior to emerging clinical observations.

Organizational Affiliation

Institut für Biochemie, Universit?t Greifswald, Greifswald, Germany.

Macromolecule Content

Total Structure Weight: 185.27 kDa
Atom Count: 11,961
Modelled Residue Count: 1,468
Deposited Residue Count: 1,592
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
TETX2 PROTEIN	A, B, C, D	398	Bacteroides thetaiotaomicron	Mutation(s): 0 EC: 1.14.13.231
UniProt
Find proteins for Q93L51 (Bacteroides thetaiotaomicron) Explore Q93L51 Go to UniProtKB: Q93L51
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q93L51
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
FAD Query on FAD Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain J [auth B] SDF format, chain O [auth C] SDF format, chain T [auth D] MOL2 format, chain E [auth A] MOL2 format, chain J [auth B] MOL2 format, chain O [auth C] MOL2 format, chain T [auth D] mmCIF format, chain E [auth A] mmCIF format, chain J [auth B] mmCIF format, chain O [auth C] mmCIF format, chain T [auth D]	E [auth A], J [auth B], O [auth C], T [auth D]	FLAVIN-ADENINE DINUCLEOTIDE C₂₇ H₃₃ N₉ O₁₅ P₂ VWWQXMAJTJZDQX-UYBVJOGSSA-N		Interactions Focus chain E [auth A] Focus chain J [auth B] Focus chain O [auth C] Focus chain T [auth D] Interactions & Density Focus chain E [auth A] Focus chain J [auth B] Focus chain O [auth C] Focus chain T [auth D]
I7T Query on I7T Download Ideal Coordinates CCD File SDF format, chain P [auth C] SDF format, chain U [auth D] SDF format, chain F [auth A] SDF format, chain K [auth B] MOL2 format, chain P [auth C] MOL2 format, chain U [auth D] MOL2 format, chain F [auth A] MOL2 format, chain K [auth B] mmCIF format, chain P [auth C] mmCIF format, chain U [auth D] mmCIF format, chain F [auth A] mmCIF format, chain K [auth B]	F [auth A], K [auth B], P [auth C], U [auth D]	7-IODOTETRACYCLINE C₂₁ H₂₁ I N₂ O₇ HTASTNARVGFMKI-UVPAEMEASA-N		Interactions Focus chain F [auth A] Focus chain K [auth B] Focus chain P [auth C] Focus chain U [auth D] Interactions & Density Focus chain F [auth A] Focus chain K [auth B] Focus chain P [auth C] Focus chain U [auth D]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain L [auth B] SDF format, chain N [auth B] SDF format, chain S [auth C] SDF format, chain V [auth D] SDF format, chain X [auth D] SDF format, chain G [auth A] SDF format, chain I [auth A] SDF format, chain M [auth B] SDF format, chain Q [auth C] SDF format, chain R [auth C] SDF format, chain W [auth D] MOL2 format, chain H [auth A] MOL2 format, chain L [auth B] MOL2 format, chain N [auth B] MOL2 format, chain S [auth C] MOL2 format, chain V [auth D] MOL2 format, chain X [auth D] MOL2 format, chain G [auth A] MOL2 format, chain I [auth A] MOL2 format, chain M [auth B] MOL2 format, chain Q [auth C] MOL2 format, chain R [auth C] MOL2 format, chain W [auth D] mmCIF format, chain H [auth A] mmCIF format, chain L [auth B] mmCIF format, chain N [auth B] mmCIF format, chain S [auth C] mmCIF format, chain V [auth D] mmCIF format, chain X [auth D] mmCIF format, chain G [auth A] mmCIF format, chain I [auth A] mmCIF format, chain M [auth B] mmCIF format, chain Q [auth C] mmCIF format, chain R [auth C] mmCIF format, chain W [auth D]	G [auth A] H [auth A] I [auth A] L [auth B] M [auth B] G [auth A], H [auth A], I [auth A], L [auth B], M [auth B], N [auth B], Q [auth C], R [auth C], S [auth C], V [auth D], W [auth D], X [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain Q [auth C] Focus chain R [auth C] Focus chain S [auth C] Focus chain V [auth D] Focus chain W [auth D] Focus chain X [auth D] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain Q [auth C] Focus chain R [auth C] Focus chain S [auth C] Focus chain V [auth D] Focus chain W [auth D] Focus chain X [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.37 ?
R-Value Free: 0.238
R-Value Work: 0.218
R-Value Observed: 0.219
Space Group: P 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 68.7	α = 111.1
b = 79.96	β = 90.41
c = 88	γ = 92.96

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
SCALEPACK	data scaling

Structure Validation

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Entry History

Deposition Data

Released Date: 2011-03-23

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2011-03-23
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: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Other, Refinement description

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Help and Resources

2Y6Q

Structure of the TetX monooxygenase in complex with the substrate 7- Iodtetracycline

Structural Basis for a New Tetracycline Resistance Mechanism Relying on the Tetx Monooxygenase.

Entity ID: 1

UniProt

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)