6DA6

Crystal structure of the TtnD decarboxylase from the tautomycetin biosynthesis pathway of Streptomyces griseochromogenes, apo form at 2.6 A resolution (P212121)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.59 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Biochemical and Structural Characterization of TtnD, a Prenylated FMN-Dependent Decarboxylase from the Tautomycetin Biosynthetic Pathway.

Annaval, T.Han, L.Rudolf, J.D.Xie, G.Yang, D.Chang, C.Y.Ma, M.Crnovcic, I.Miller, M.D.Soman, J.Xu, W.Phillips Jr., G.N.Shen, B.

(2018) ACS Chem Biol 13: 2728-2738

  • DOI: https://doi.org/10.1021/acschembio.8b00673
  • Primary Citation of Related Structures:  
    6DA6, 6DA7, 6DA9

  • PubMed Abstract: 

    Tautomycetin (TTN) is a polyketide natural product featuring a terminal alkene. Functional characterization of the genes within the ttn gene cluster from Streptomyces griseochromogenes established the biosynthesis of the TTN polyketide backbone, its dialkylmaleic anhydride moiety, the coupling of the two moieties to form the nascent intermediate TTN F-1, and the tailoring steps converting TTN F-1 to TTN. Here, we report biochemical and structural characterization of TtnD, a prenylated FMN (prFMN)-dependent decarboxylase belonging to the UbiD family that catalyzes the penultimate step of TTN biosynthesis. TtnD catalyzes decarboxylation of TTN D-1 to TTN I-1, utilizing prFMN as a cofactor generated by the TtnC flavin prenyltransferase; both TtnD and TtnC are encoded within the ttn biosynthetic gene cluster. TtnD exhibits substrate promiscuity but accepts only TTN D-1 congeners that feature an α,β-unsaturated acid, supporting the [3+2] cycloaddition mechanism during catalysis that requires the double bond of an α,β-unsaturated acid substrate. TtnD shares a similar overall structure with other members of the UbiD family but forms a homotetramer in solution. Each protomer is composed of three domains with the active site located between the middle and C-terminal domains; R169-E272-E277, constituting the catalytic triad, and E228, involved in Mn(II)-mediated binding of prFMN, were confirmed by site-directed mutagenesis. TtnD represents the first example of a prFMN-dependent decarboxylase involved in polyketide biosynthesis, expanding the substrate scope of the UbiD family of decarboxylases beyond simple aromatic and cinnamic acids. TtnD and its homologues are widespread in nature and could be exploited as biocatalysts for organic synthesis.


  • Organizational Affiliation

    Department of Chemistry , The Scripps Research Institute , 130 Scripps Way , Jupiter , Florida 33458 , United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UbiD-like decarboxylase
A, B, C, D
501Streptomyces griseochromogenesMutation(s): 0 
Gene Names: ttnD
EC: 4.1.1
UniProt
Find proteins for C6ZCR8 (Streptomyces griseochromogenes)
Explore C6ZCR8 
Go to UniProtKB:  C6ZCR8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupC6ZCR8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B],
R [auth C],
S [auth C],
T [auth C],
U [auth C],
W [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A],
Q [auth B],
Y [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
UNL
Query on UNL

Download Ideal Coordinates CCD File 
V [auth C],
X [auth D]
Unknown ligand
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.59 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.215α = 90
b = 137.117β = 90
c = 284.074γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
XDSdata scaling
PHASERphasing
BUSTERrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesU01GM098248

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-03
    Type: Initial release
  • Version 1.1: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description