1Q3G

MurA (Asp305Ala) liganded with tetrahedral reaction intermediate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 

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Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

A New View of the Mechanisms of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) and 5-Enolpyruvylshikimate-3-phosphate Synthase (AroA) Derived from X-ray Structures of Their Tetrahedral Reaction Intermediate States.

Eschenburg, S.Kabsch, W.Healy, M.L.Schonbrunn, E.

(2003) J Biol Chem 278: 49215-49222

  • DOI: https://doi.org/10.1074/jbc.M309741200
  • Primary Citation of Related Structures:  
    1Q36, 1Q3G

  • PubMed Abstract: 

    UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) constitute the small enzyme family of enolpyruvyl transferases, which catalyze the chemically unusual reaction of enolpyruvyl transfer. MurA catalyzes the first step in the biosynthesis of the bacterial cell wall; AroA is the sixth enzyme of the shikimate pathway leading to the synthesis of aromatic compounds in numerous microorganisms and plants. Because both metabolic pathways are absent from mammals but essential for the growth of microorganisms, MurA and AroA are attractive targets for the development of novel antimicrobial drugs. We have determined the x-ray structures of the D305A mutant of Enterobacter cloacae MurA and the D313A mutant of Escherichia coli AroA, both of which crystallized in the presence of their substrates. The structures depict the tetrahedral reaction intermediate states of the enzymes and prove that, without the aspartate side chain, the overall addition-elimination reaction in both enzymes is halted after the addition step. The presented structures lead to a new view of the catalytic mechanism and, moreover, provide an ideal starting point for the rational design of potent inhibitors of MurA and AroA.


  • Organizational Affiliation

    Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, USA. eschoenb@ku.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UDP-N-acetylglucosamine 1-carboxyvinyltransferase419Enterobacter cloacaeMutation(s): 2 
Gene Names: MURA
EC: 2.5.1.7
UniProt
Find proteins for P33038 (Enterobacter cloacae subsp. cloacae (strain ATCC 13047 / DSM 30054 / NBRC 13535 / NCTC 10005 / WDCM 00083 / NCDC 279-56))
Explore P33038 
Go to UniProtKB:  P33038
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP33038
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UDA
Query on UDA

Download Ideal Coordinates CCD File 
AA [auth F]
CA [auth G]
EA [auth H]
GA [auth I]
IA [auth J]
AA [auth F],
CA [auth G],
EA [auth H],
GA [auth I],
IA [auth J],
KA [auth K],
MA [auth L],
OA [auth W],
Q [auth A],
QA [auth X],
S [auth B],
SA [auth Y],
U [auth C],
UA [auth Z],
W [auth D],
Y [auth E]
3'-1-CARBOXY-1-PHOSPHONOOXY-ETHOXY-URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE
C20 H32 N3 O23 P3
NLBIPGBVVPCESQ-BVDGEXFOSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
BA [auth F]
DA [auth G]
FA [auth H]
HA [auth I]
JA [auth J]
BA [auth F],
DA [auth G],
FA [auth H],
HA [auth I],
JA [auth J],
LA [auth K],
NA [auth L],
PA [auth W],
R [auth A],
RA [auth X],
T [auth B],
TA [auth Y],
V [auth C],
VA [auth Z],
X [auth D],
Z [auth E]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 139.459α = 90
b = 153.934β = 112.95
c = 167.481γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
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: 2003-12-16
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2011-07-27
    Changes: Database references, Derived calculations, Non-polymer description
  • Version 1.4: 2017-10-11
    Changes: Advisory, Refinement description
  • Version 1.5: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.6: 2023-08-16
    Changes: Data collection, Refinement description