3ISS

Crystal structure of enolpyruvyl-UDP-GlcNAc synthase (MurA):UDP-N-acetylmuramic acid:phosphite from Escherichia coli


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history

Re-refinement Note

A newer entry is available that reflects an alternative modeling of the original data: 3SWD


Literature

Evidence of Kinetic Control of Ligand Binding and Staged Product Release in MurA (Enolpyruvyl UDP-GlcNAc Synthase)-Catalyzed Reactions .

Jackson, S.G.Zhang, F.Chindemi, P.Junop, M.S.Berti, P.J.

(2009) Biochemistry 48: 11715-11723

  • DOI: https://doi.org/10.1021/bi901524q
  • Primary Citation of Related Structures:  
    3ISS

  • PubMed Abstract: 

    MurA (enolpyruvyl UDP-GlcNAc synthase) catalyzes the first committed step in peptidoglycan biosynthesis. In this study, MurA-catalyzed breakdown of its tetrahedral intermediate (THI), with a k(cat)/K(M) of 520 M(-1) s(-1), was far slower than the normal reaction, and 3 x 10(5)-fold slower than the homologous enzyme, AroA, reacting with its THI. This provided kinetic evidence of slow binding and a conformationally constrained active site. The MurA cocrystal structure with UDP-N-acetylmuramic acid (UDP-MurNAc), a potent inhibitor, and phosphite revealed a new "staged" MurA conformation in which the Arg397 side chain tracked phosphite out of the catalytic site. The closed-to-staged transition involved breaking eight MurA.ligand ion pairs, and three intraprotein hydrogen bonds helping hold the active site loop closed. These were replaced with only two MurA.UDP-MurNAc ion pairs, two with phosphite, and seven new intraprotein ion pairs or hydrogen bonds. Cys115 appears to have an important role in forming the staged conformation. The staged conformation appears to be one step in a complex choreography of release of the product from MurA.


  • Organizational Affiliation

    Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton,Ontario L8S 4M1, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L
418Escherichia coli K-12Mutation(s): 1 
Gene Names: b3189JW3156murAmurZ
EC: 2.5.1.7
UniProt
Find proteins for P0A749 (Escherichia coli (strain K12))
Explore P0A749 
Go to UniProtKB:  P0A749
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0A749
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EPU
Query on EPU

Download Ideal Coordinates CCD File 
BA [auth H]
DA [auth I]
FA [auth J]
HA [auth K]
JA [auth L]
BA [auth H],
DA [auth I],
FA [auth J],
HA [auth K],
JA [auth L],
N [auth A],
P [auth B],
R [auth C],
T [auth D],
V [auth E],
X [auth F],
Z [auth G]
URIDINE-DIPHOSPHATE-2(N-ACETYLGLUCOSAMINYL) BUTYRIC ACID
C20 H29 N3 O19 P2
BEGZZYPUNCJHKP-DBYWSUQTSA-N
PO3
Query on PO3

Download Ideal Coordinates CCD File 
AA [auth H]
CA [auth I]
EA [auth J]
GA [auth K]
IA [auth L]
AA [auth H],
CA [auth I],
EA [auth J],
GA [auth K],
IA [auth L],
M [auth A],
O [auth B],
Q [auth C],
S [auth D],
U [auth E],
W [auth F],
Y [auth G]
PHOSPHITE ION
O3 P
AQSJGOWTSHOLKH-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EPU PDBBind:  3ISS Ki: 900 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.223 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.51α = 111.52
b = 120.91β = 104.44
c = 139.73γ = 90.19
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
PHENIXrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-11-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-07-27
    Changes: Database references, Derived calculations, Non-polymer description
  • Version 1.3: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-09-06
    Changes: Data collection, Refinement description