1KFL

Crystal structure of phenylalanine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHP synthase) from E.coli complexed with Mn2+, PEP, and Phe


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.219 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Allosteric inhibition of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase alters the coordination of both substrates.

Shumilin, I.A.Zhao, C.Bauerle, R.Kretsinger, R.H.

(2002) J Mol Biol 320: 1147-1156

  • DOI: https://doi.org/10.1016/s0022-2836(02)00545-4
  • Primary Citation of Related Structures:  
    1KFL

  • PubMed Abstract: 

    3-Deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS), the first enzyme of the aromatic biosynthetic pathway in microorganisms and plants, catalyzes the aldol-like condensation of phosphoenolpyruvate and D-erythrose-4-phosphate with the formation of 3-deoxy-D-arabino-heptulosonate-7-phosphate. In Escherichia coli, there are three isoforms of DAHPS, each specifically feedback-regulated by one of the three aromatic amino acid end products. The crystal structure of the phenylalanine-regulated DAHPS from E.coli in complex with its inhibitor, L-phenylalanine, phosphoenolpyruvate, and metal cofactor, Mn(2+), has been determined to 2.8A resolution. Phe binds in a cavity formed by residues of two adjacent subunits and is located about 20A from the closest active site. A model for the mechanism of allosteric inhibition has been derived from conformational differences between the Phe-bound and previously determined Phe-free structures. Two interrelated paths of conformational changes transmit the inhibitory signal from the Phe-binding site to the active site of DAHPS. The first path involves transmission within a single subunit due to the movement of adjacent segments of the protein. The second involves alterations in the contacts between subunits. The combination of these two paths changes the conformation of one of the active site loops significantly and shifts the other slightly. This alters the interaction of DAHPS with both of its substrates. Upon binding of Phe, the enzyme loses the ability to bind D-erythrose-4-phosphate and binds phosphoenolpyruvate in a flipped orientation.


  • Organizational Affiliation

    Department of Biology, University of Virginia, Charlottesville, VA 22903, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-deoxy-D-arabino-heptulosonate-7-phosphate synthase
A, B, C, D, E
A, B, C, D, E, F, G, H
350Escherichia coliMutation(s): 0 
Gene Names: aroG
EC: 4.1.2.15
UniProt
Find proteins for P0AB91 (Escherichia coli (strain K12))
Explore P0AB91 
Go to UniProtKB:  P0AB91
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0AB91
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PEP
Query on PEP

Download Ideal Coordinates CCD File 
BA [auth D]
GA [auth E]
LA [auth F]
M [auth A]
PA [auth G]
BA [auth D],
GA [auth E],
LA [auth F],
M [auth A],
PA [auth G],
R [auth B],
VA [auth H],
W [auth C]
PHOSPHOENOLPYRUVATE
C3 H5 O6 P
DTBNBXWJWCWCIK-UHFFFAOYSA-N
PHE
Query on PHE

Download Ideal Coordinates CCD File 
AA [auth D]
FA [auth E]
KA [auth F]
L [auth A]
OA [auth G]
AA [auth D],
FA [auth E],
KA [auth F],
L [auth A],
OA [auth G],
Q [auth B],
UA [auth H],
V [auth C]
PHENYLALANINE
C9 H11 N O2
COLNVLDHVKWLRT-QMMMGPOBSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
DA [auth E]
EA [auth E]
IA [auth F]
J [auth A]
JA [auth F]
DA [auth E],
EA [auth E],
IA [auth F],
J [auth A],
JA [auth F],
K [auth A],
NA [auth G],
O [auth B],
P [auth B],
RA [auth H],
SA [auth H],
T [auth C],
TA [auth H],
U [auth C],
Y [auth D],
Z [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
MN
Query on MN

Download Ideal Coordinates CCD File 
CA [auth E]
HA [auth F]
I [auth A]
MA [auth G]
N [auth B]
CA [auth E],
HA [auth F],
I [auth A],
MA [auth G],
N [auth B],
QA [auth H],
S [auth C],
X [auth D]
MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B, C, D, E
A, B, C, D, E, F, G, H
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.219 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 290.097α = 90
b = 90.097β = 120.77
c = 155.798γ = 90
Software Package:
Software NamePurpose
MLPHAREphasing
DMmodel building
CNSrefinement
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
CCP4data scaling
DMphasing
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-08-23
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-11-15
    Changes: Data collection