5JRH

Crystal structure of Salmonella enterica acetyl-CoA synthetase (Acs) in complex with cAMP and Coenzyme A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.64 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.171 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Cyclic AMP Inhibits the Activity and Promotes the Acetylation of Acetyl-CoA Synthetase through Competitive Binding to the ATP/AMP Pocket.

Han, X.Shen, L.Wang, Q.Cen, X.Wang, J.Wu, M.Li, P.Zhao, W.Zhang, Y.Zhao, G.

(2017) J Biol Chem 292: 1374-1384

  • DOI: https://doi.org/10.1074/jbc.M116.753640
  • Primary Citation of Related Structures:  
    5JRH

  • PubMed Abstract: 

    The high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. In this study, we discovered that cAMP directly binds to Salmonella enterica Acs (SeAcs) and inhibits its activity in a substrate-competitive manner. In addition, cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition. A crystal structure study and site-directed mutagenesis analyses confirmed that cAMP binds to the ATP/AMP pocket of SeAcs, and restrains SeAcs in an open conformation. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs.


  • Organizational Affiliation

    From the Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acetyl-coenzyme A synthetase
A, B
660Salmonella enterica subsp. enterica serovar Typhimurium str. LT2Mutation(s): 0 
Gene Names: acsSTM4275
EC: 6.2.1.1
UniProt
Find proteins for Q8ZKF6 (Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720))
Explore Q8ZKF6 
Go to UniProtKB:  Q8ZKF6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8ZKF6
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
COA
Query on COA

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
COENZYME A
C21 H36 N7 O16 P3 S
RGJOEKWQDUBAIZ-IBOSZNHHSA-N
CMP
Query on CMP

Download Ideal Coordinates CCD File 
D [auth A],
I [auth B]
ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE
C10 H12 N5 O6 P
IVOMOUWHDPKRLL-KQYNXXCUSA-N
BU3
Query on BU3

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
K [auth B],
L [auth B]
(R,R)-2,3-BUTANEDIOL
C4 H10 O2
OWBTYPJTUOEWEK-QWWZWVQMSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A],
J [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.64 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.171 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.193α = 90
b = 144.339β = 91.73
c = 71.734γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Natural Science Foundation for YouthChina31400039
Postdoctoral Science Foundation of ChinaChina2012M510787

Revision History  (Full details and data files)

  • Version 1.0: 2016-12-21
    Type: Initial release
  • Version 1.1: 2017-12-06
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description