5CKV

DAHP synthase from Mycobacterium tuberculosis, fully inhibited by tyrosine, phenylalanine, and tryptophan


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Remote Control by Inter-Enzyme Allostery: A Novel Paradigm for Regulation of the Shikimate Pathway.

Munack, S.Roderer, K.Okvist, M.Kamarauskaite, J.Sasso, S.van Eerde, A.Kast, P.Krengel, U.

(2016) J Mol Biol 428: 1237-1255

  • DOI: https://doi.org/10.1016/j.jmb.2016.01.001
  • Primary Citation of Related Structures:  
    5CKV, 5CKX

  • PubMed Abstract: 

    DAHP synthase and chorismate mutase catalyze key steps in the shikimate biosynthetic pathway en route to aromatic amino acids. In Mycobacterium tuberculosis, chorismate mutase (MtCM; Rv0948c), located at the branch point toward phenylalanine and tyrosine, has poor activity on its own. However, it is efficiently activated by the first enzyme of the pathway, DAHP synthase (MtDS; Rv2178c), through formation of a non-covalent MtCM-MtDS complex. Here, we show how MtDS serves as an allosteric platform for feedback regulation of both enzymes, using X-ray crystallography, small-angle X-ray scattering, size-exclusion chromatography, and multi-angle light scattering. Crystal structures of the fully inhibited MtDS and the allosterically down-regulated MtCM-MtDS complex, solved at 2.8 and 2.7Å, respectively, reveal how effector binding at the internal MtDS subunit interfaces regulates the activity of MtDS and MtCM. While binding of all three metabolic end products to MtDS shuts down the entire pathway, the binding of phenylalanine jointly with tyrosine releases MtCM from the MtCM-MtDS complex, hence suppressing MtCM activation by 'inter-enzyme allostery'. This elegant regulatory principle, invoking a transient allosteric enzyme interaction, seems to be driven by dynamics and is likely a general strategy used by nature.


  • Organizational Affiliation

    Department of Chemistry, University of Oslo, NO-0315 Oslo, Norway.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phospho-2-dehydro-3-deoxyheptonate aldolase AroG
A, B
472Mycobacterium tuberculosisMutation(s): 0 
Gene Names: aroGRv2178c
EC: 2.5.1.54
UniProt
Find proteins for O53512 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore O53512 
Go to UniProtKB:  O53512
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO53512
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TRP
Query on TRP

Download Ideal Coordinates CCD File 
I [auth A],
T [auth B]
TRYPTOPHAN
C11 H12 N2 O2
QIVBCDIJIAJPQS-VIFPVBQESA-N
TYR
Query on TYR

Download Ideal Coordinates CCD File 
S [auth B]TYROSINE
C9 H11 N O3
OUYCCCASQSFEME-QMMMGPOBSA-N
PHE
Query on PHE

Download Ideal Coordinates CCD File 
K [auth A],
U [auth B]
PHENYLALANINE
C9 H11 N O2
COLNVLDHVKWLRT-QMMMGPOBSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
N [auth B],
O [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
P [auth B],
Q [auth B],
R [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
MN
Query on MN

Download Ideal Coordinates CCD File 
J [auth A],
M [auth B]
MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A],
L [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 204.76α = 90
b = 204.76β = 90
c = 66.774γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Research Council of NorwayNorway143645
Swiss National Science FoundationSwitzerland31003A-116475, 31003A-135651, and 31003A_156453

Revision History  (Full details and data files)

  • Version 1.0: 2016-01-27
    Type: Initial release
  • Version 1.1: 2016-04-20
    Changes: Database references
  • Version 1.2: 2018-01-31
    Changes: Author supporting evidence
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description