RCSB PDB - 8EGY: Engineered holo tyrosine synthase (TmTyrS1) derived from T. maritima TrpB

 8EGY

Engineered holo tyrosine synthase (TmTyrS1) derived from T. maritima TrpB


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

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This is version 1.2 of the entry. See complete history


Literature

The beta-subunit of tryptophan synthase is a latent tyrosine synthase.

Almhjell, P.J.Johnston, K.E.Porter, N.J.Kennemur, J.L.Bhethanabotla, V.C.Ducharme, J.Arnold, F.H.

(2024) Nat Chem Biol 20: 1086-1093

  • DOI: https://doi.org/10.1038/s41589-024-01619-z
  • Primary Citation of Related Structures:  
    8EGY, 8EGZ, 8EH0, 8EH1

  • PubMed Abstract: 

    Aromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we introduce a new enzymatic transformation for L-tyrosine synthesis by demonstrating that the β-subunit of tryptophan synthase-which natively couples indole and L-serine to form L-tryptophan-can act as a latent 'tyrosine synthase'. A single substitution of a near-universally conserved catalytic residue unlocks activity toward simple phenol analogs and yields exclusive para carbon-carbon bond formation to furnish L-tyrosines. Structural and mechanistic studies show how a new active-site water molecule orients phenols for a nonnative mechanism of alkylation, with additional directed evolution resulting in a net >30,000-fold rate enhancement. This new biocatalyst can be used to efficiently prepare valuable L-tyrosine analogs at gram scales and provides the missing chemistry for a conceptually different pathway to L-tyrosine.


  • Organizational Affiliation

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tryptophan synthase beta chain 1
A, B
397Thermotoga maritimaMutation(s): 18 
Gene Names: trpB1trpBTM_0138
EC: 4.2.1.20
UniProt
Find proteins for P50909 (Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8))
Explore P50909 
Go to UniProtKB:  P50909
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50909
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLP (Subject of Investigation/LOI)
Query on PLP

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
G [auth A],
K [auth B]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
EDO
Query on EDO

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
J [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
D [auth A],
I [auth B]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.217 
  • Space Group: I 4
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 164.606α = 90
b = 164.606β = 90
c = 83.139γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted PLPClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM125887

Revision History  (Full details and data files)

  • Version 1.0: 2023-10-04
    Type: Initial release
  • Version 1.1: 2024-07-03
    Changes: Database references
  • Version 1.2: 2024-08-14
    Changes: Database references