5KZM

Crystal structure of Tryptophan synthase alpha-beta chain complex from Francisella tularensis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.186 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Conservation of the structure and function of bacterial tryptophan synthases.

Michalska, K.Gale, J.Joachimiak, G.Chang, C.Hatzos-Skintges, C.Nocek, B.Johnston, S.E.Bigelow, L.Bajrami, B.Jedrzejczak, R.P.Wellington, S.Hung, D.T.Nag, P.P.Fisher, S.L.Endres, M.Joachimiak, A.

(2019) IUCrJ 6: 649-664

  • DOI: https://doi.org/10.1107/S2052252519005955
  • Primary Citation of Related Structures:  
    5KIN, 5KZM

  • PubMed Abstract: 

    Tryptophan biosynthesis is one of the most characterized processes in bacteria, in which the enzymes from Salmonella typhimurium and Escherichia coli serve as model systems. Tryptophan synthase (TrpAB) catalyzes the final two steps of tryptophan biosynthesis in plants, fungi and bacteria. This pyridoxal 5'-phosphate (PLP)-dependent enzyme consists of two protein chains, α (TrpA) and β (TrpB), functioning as a linear αββα heterotetrameric complex containing two TrpAB units. The reaction has a complicated, multistep mechanism resulting in the β-replacement of the hydroxyl group of l-serine with an indole moiety. Recent studies have shown that functional TrpAB is required for the survival of pathogenic bacteria in macrophages and for evading host defense. Therefore, TrpAB is a promising target for drug discovery, as its orthologs include enzymes from the important human pathogens Streptococcus pneumoniae , Legionella pneumophila and Francisella tularensis , the causative agents of pneumonia, legionnaires' disease and tularemia, respectively. However, specific biochemical and structural properties of the TrpABs from these organisms have not been investigated. To fill the important phylogenetic gaps in the understanding of TrpABs and to uncover unique features of TrpAB orthologs to spearhead future drug-discovery efforts, the TrpABs from L. pneumophila , F. tularensis and S. pneumoniae have been characterized. In addition to kinetic properties and inhibitor-sensitivity data, structural information gathered using X-ray crystallo-graphy is presented. The enzymes show remarkable structural conservation, but at the same time display local differences in both their catalytic and allosteric sites that may be responsible for the observed differences in catalysis and inhibitor binding. This functional dissimilarity may be exploited in the design of species-specific enzyme inhibitors.


  • Organizational Affiliation

    Center for Structural Genomics of Infectious Diseases, University of Chicago, Chicago, IL 60367, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tryptophan synthase alpha chain272Francisella tularensis subsp. tularensis SCHU S4Mutation(s): 0 
Gene Names: trpAFTT_1772c
EC: 4.2.1.20
UniProt
Find proteins for Q5NE80 (Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4))
Explore Q5NE80 
Go to UniProtKB:  Q5NE80
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5NE80
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tryptophan synthase beta chain396Francisella tularensis subsp. tularensis SCHU S4Mutation(s): 0 
Gene Names: trpBFTT_1773c
EC: 4.2.1.20
UniProt
Find proteins for Q5NE79 (Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4))
Explore Q5NE79 
Go to UniProtKB:  Q5NE79
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5NE79
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
LLP
Query on LLP
B
L-PEPTIDE LINKINGC14 H22 N3 O7 PLYS
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.176α = 90
b = 171.986β = 90
c = 76.109γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction
HKL-3000data scaling
HKL-3000phasing

Structure Validation

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Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-10
    Type: Initial release
  • Version 1.1: 2016-09-07
    Changes: Database references, Structure summary
  • Version 2.0: 2018-05-09
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Polymer sequence, Source and taxonomy, Structure summary
  • Version 2.1: 2019-09-18
    Changes: Data collection, Database references