4B0J

Crystal Structure of 3-hydroxydecanoyl-Acyl Carrier Protein Dehydratase (FabA) from Pseudomonas aeruginosa in complex with 5-(2- thienyl)-3-isoxazolyl methanol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.235 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural Insights Into the Mechanism and Inhibition of the Beta-Hydroxydecanoyl-Acyl Carrier Protein Dehydratase from Pseudomonas Aeruginosa

Moynie, L.Leckie, S.M.Mcmahon, S.A.Duthie, F.G.Koehnke, A.Taylor, J.W.Alphey, M.S.Brenk, R.Smith, A.D.Naismith, J.H.

(2013) J Mol Biol 425: 365-377

  • DOI: https://doi.org/10.1016/j.jmb.2012.11.017
  • Primary Citation of Related Structures:  
    4B0B, 4B0C, 4B0I, 4B0J, 4B8U, 4FQ9

  • PubMed Abstract: 

    Fatty acid biosynthesis is an essential component of metabolism in both eukaryotes and prokaryotes. The fatty acid biosynthetic pathway of Gram-negative bacteria is an established therapeutic target. Two homologous enzymes FabA and FabZ catalyze a key step in fatty acid biosynthesis; both dehydrate hydroxyacyl fatty acids that are coupled via a phosphopantetheine to an acyl carrier protein (ACP). The resulting trans-2-enoyl-ACP is further polymerized in a processive manner. FabA, however, carries out a second reaction involving isomerization of trans-2-enoyl fatty acid to cis-3-enoyl fatty acid. We have solved the structure of Pseudomonas aeruginosa FabA with a substrate allowing detailed molecular insight into the interactions of the active site. This has allowed a detailed examination of the factors governing the second catalytic step. We have also determined the structure of FabA in complex with small molecules (so-called fragments). These small molecules occupy distinct regions of the active site and form the basis for a rational inhibitor design program.


  • Organizational Affiliation

    Biomedical Sciences Research Complex, The University, St. Andrews KY16 9ST, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-HYDROXYDECANOYL-[ACYL-CARRIER-PROTEIN] DEHYDRATASE
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T
171Pseudomonas aeruginosa PAO1Mutation(s): 0 
EC: 4.2.1.60
UniProt
Find proteins for O33877 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1))
Explore O33877 
Go to UniProtKB:  O33877
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO33877
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3MQ
Query on 3MQ

Download Ideal Coordinates CCD File 
AA [auth G]
BA [auth H]
CA [auth I]
DA [auth J]
EA [auth K]
AA [auth G],
BA [auth H],
CA [auth I],
DA [auth J],
EA [auth K],
FA [auth L],
GA [auth M],
HA [auth N],
IA [auth O],
JA [auth P],
KA [auth Q],
LA [auth R],
MA [auth S],
NA [auth T],
U [auth A],
V [auth B],
W [auth C],
X [auth D],
Y [auth E],
Z [auth F]
(5-thiophen-2-ylisoxazol-3-yl)methanol
C8 H7 N O2 S
HUAGDHXVPCSWLD-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3MQ PDBBind:  4B0J Kd: 7.10e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.235 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.753α = 90
b = 108.17β = 103.22
c = 201.766γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-11-28
    Type: Initial release
  • Version 1.1: 2013-01-30
    Changes: Database references
  • Version 1.2: 2013-09-04
    Changes: Atomic model, Derived calculations, Non-polymer description, Other
  • Version 1.3: 2018-06-13
    Changes: Data collection, Database references
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description