4IHG

Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Chasing acyl carrier protein through a catalytic cycle of lipid A production.

Masoudi, A.Raetz, C.R.Zhou, P.Pemble, C.W.

(2014) Nature 505: 422-426

  • DOI: https://doi.org/10.1038/nature12679
  • Primary Citation of Related Structures:  
    4IHF, 4IHG, 4IHH

  • PubMed Abstract: 

    Acyl carrier protein represents one of the most highly conserved proteins across all domains of life and is nature's way of transporting hydrocarbon chains in vivo. Notably, type II acyl carrier proteins serve as a crucial interaction hub in primary cellular metabolism by communicating transiently between partner enzymes of the numerous biosynthetic pathways. However, the highly transient nature of such interactions and the inherent conformational mobility of acyl carrier protein have stymied previous attempts to visualize structurally acyl carrier protein tied to an overall catalytic cycle. This is essential to understanding a fundamental aspect of cellular metabolism leading to compounds that are not only useful to the cell, but also of therapeutic value. For example, acyl carrier protein is central to the biosynthesis of the lipid A (endotoxin) component of lipopolysaccharides in Gram-negative microorganisms, which is required for their growth and survival, and is an activator of the mammalian host's immune system, thus emerging as an important therapeutic target. During lipid A synthesis (Raetz pathway), acyl carrier protein shuttles acyl intermediates linked to its prosthetic 4'-phosphopantetheine group among four acyltransferases, including LpxD. Here we report the crystal structures of three forms of Escherichia coli acyl carrier protein engaging LpxD, which represent stalled substrate and liberated products along the reaction coordinate. The structures show the intricate interactions at the interface that optimally position acyl carrier protein for acyl delivery and that directly involve the pantetheinyl group. Conformational differences among the stalled acyl carrier proteins provide the molecular basis for the association-dissociation process. An unanticipated conformational shift of 4'-phosphopantetheine groups within the LpxD catalytic chamber shows an unprecedented role of acyl carrier protein in product release.


  • Organizational Affiliation

    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase
A, B, C, D, E
A, B, C, D, E, F
348Escherichia coli K-12Mutation(s): 0 
Gene Names: lpxDfirAomsAb0179JW0174
EC: 2.3.1.191
UniProt
Find proteins for P21645 (Escherichia coli (strain K12))
Explore P21645 
Go to UniProtKB:  P21645
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21645
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Acyl carrier protein
G, H, I, J, K
G, H, I, J, K, L
80Escherichia coli str. 'clone D i14Mutation(s): 0 
Gene Names: acpPi14_1248
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PNS
Query on PNS

Download Ideal Coordinates CCD File 
U [auth G]
V [auth H]
W [auth I]
X [auth J]
Y [auth K]
U [auth G],
V [auth H],
W [auth I],
X [auth J],
Y [auth K],
Z [auth L]
4'-PHOSPHOPANTETHEINE
C11 H23 N2 O7 P S
JDMUPRLRUUMCTL-VIFPVBQESA-N
FTT
Query on FTT

Download Ideal Coordinates CCD File 
M [auth A]
N [auth B]
O [auth B]
P [auth C]
Q [auth D]
M [auth A],
N [auth B],
O [auth B],
P [auth C],
Q [auth D],
R [auth E],
S [auth E],
T [auth F]
3-HYDROXY-TETRADECANOIC ACID
C14 H28 O3
ATRNZOYKSNPPBF-CYBMUJFWSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.18α = 104.09
b = 89.31β = 92.58
c = 111.933γ = 118.64
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
SERGUIdata collection
HKL-2000data reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-13
    Type: Initial release
  • Version 1.1: 2013-11-20
    Changes: Database references
  • Version 1.2: 2014-01-22
    Changes: Database references
  • Version 1.3: 2014-01-29
    Changes: Database references
  • Version 1.4: 2017-11-15
    Changes: Refinement description