8AD7

Flavin-dependent tryptophan 6-halogenase Thal in complex with D-Trp


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.192 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Enzymatic Late-Stage Halogenation of Peptides.

Schnepel, C.Moritzer, A.C.Gafe, S.Montua, N.Minges, H.Niess, A.Niemann, H.H.Sewald, N.

(2023) Chembiochem 24: e202200569-e202200569

  • DOI: https://doi.org/10.1002/cbic.202200569
  • Primary Citation of Related Structures:  
    8AD7, 8AD8

  • PubMed Abstract: 

    The late-stage site-selective derivatisation of peptides has many potential applications in structure-activity relationship studies and postsynthetic modification or conjugation of bioactive compounds. The development of orthogonal methods for C-H functionalisation is crucial for such peptide derivatisation. Among them, biocatalytic methods are increasingly attracting attention. Tryptophan halogenases emerged as valuable catalysts to functionalise tryptophan (Trp), while direct enzyme-catalysed halogenation of synthetic peptides is yet unprecedented. Here, it is reported that the Trp 6-halogenase Thal accepts a wide range of amides and peptides containing a Trp moiety. Increasing the sequence length and reaction optimisation made bromination of pentapeptides feasible with good turnovers and a broad sequence scope, while regioselectivity turned out to be sequence dependent. Comparison of X-ray single crystal structures of Thal in complex with d-Trp and a dipeptide revealed a significantly altered binding mode for the peptide. The viability of this bioorthogonal approach was exemplified by halogenation of a cyclic RGD peptide.


  • Organizational Affiliation

    Organische und Bioorganische Chemie, Fakultät für Chemie, Universität Bielefeld, Universitätsstraße 25, 33615, Bielefeld, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tryptophan 6-halogenase
A, B
534Streptomyces albogriseolusMutation(s): 0 
Gene Names: thalthdH
EC: 1.14.19.59
UniProt
Find proteins for A1E280 (Streptomyces albogriseolus)
Explore A1E280 
Go to UniProtKB:  A1E280
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA1E280
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DTR (Subject of Investigation/LOI)
Query on DTR

Download Ideal Coordinates CCD File 
J [auth A]D-TRYPTOPHAN
C11 H12 N2 O2
QIVBCDIJIAJPQS-SECBINFHSA-N
PO4
Query on PO4

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

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
K [auth B]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
K [auth B],
L [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 138.91α = 90
b = 138.91β = 90
c = 142.59γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Not funded--

Revision History  (Full details and data files)

  • Version 1.0: 2022-10-12
    Type: Initial release
  • Version 1.1: 2022-11-02
    Changes: Database references
  • Version 1.2: 2022-12-07
    Changes: Database references
  • Version 1.3: 2023-01-11
    Changes: Database references
  • Version 1.4: 2024-01-31
    Changes: Data collection, Refinement description