Structure of IDP00816
1.82 Angstrom resolution crystal structure of holo-(acyl- carrier-protein) synthase (ACPS) from Staphylococcus aureus
- CSGID target
- IDP00816
- PDB Id
- 3F09 (NCBI MMDB)
- Authors
- A.S.Halavaty,G.Minasov,L.Shuvalova,I.Dubrovska,L.Papazisi,W.F.Anderson,Center For Structural Genomics Of Infectious Diseases (Csgid)
- Responsible person
- Andrei Halavaty
- Responsible lab
- Northwestern University
- Deposition Date
- Oct 24, 2008
- Release Date
- Nov 11, 2008
Annotation
- Description
- Fatty acids are essential components of bacterial membrane lipids and lipopolysaccharides that are required for microbial growth. An acyl carrier protein synthase (AcpS) plays important role in biosynthesis pathway of fatty acids by catalyzing the Mg2+-dependent transfer of the 4'-phosphopantotheine moiety of the coenzyme A (CoA) onto a conserved serine residue of a newly synthesized inactive acyl carrier protein (ACP). This post-translational modification results in conversion of apo-ACP to a functional holo-ACP that then transfers acyl fatty acid intermediates in the pathway. Inhibition of fatty acid biosynthetic enzymes may not be effective in preventing bacterial growth in vivo, because fatty acids are readily available from the host. AcpS will be functional in lipid biosynthesis. Therefore, targeting the synthase can be a better approach to inhibiting bacterial growth. AcpS-like proteins form either a functional dimeric or trimeric quaternary structures. AcpS from S. aureus is a trimer as revealed by dynamic light scattering measurement and structure solution. Formation of the trimer is facilitated by the amphipatic nature of three copies of an antiparallel b sheet resulting in a central b-barrel. CoA and its derivatives are native cofactors of the AcpS enzymes binding at the solvent-exposed interface between monomers in these oligomeric proteins. In the 3F09 structure no coenzyme is observed. Since the coenzyme’s binding site is highly conserved among AcpS enzymes, especially for ATP part of CoA, similar interaction mode of the cofactor with the ApcS from Staphylococcus is expected. Successful crystallization and structure determination of AcpS in complex with its native apo-ACP and in the presence of CoA will provide us with details of the mechanism of the reaction and assist in the design of broad-spectrum of antibiotics for inhibition. For this inactivation purpose, ligand screening will be also then required. Moreover, it is suggested that even ACP at high concentrations may also serve as an inhibitor of CoA binding and, hence, preventing the cleavage of the prosthetic group. These facts can additionally broad our inhibition strategies.
- Functional assignment
- Transferase
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Ligands
| Ligand code | Name | Ligand type |
|---|
Structure information
Unit cell parameters
- Space Group
- P 21 21 21
- Unit Cell
-
a=67.39Å, b=77.40Å, c=81.50Å
α=90.00, β=90.00, γ=90.00 - Solvent content
- 43.16
- Matthews coefficient
- 2.16
- Resolution range
- 28.89-1.82Å (1.87-1.82Å)
- Rall(%)
- 18.6
- Rwork(%)
- 18.4 (24.2)
- Rfree(%)
- 22.5 (28.1)
- Num. observed reflections
- 37920 (2553)
- Num. Rfree reflections
- 1896 (129)
- Completeness(%)
- 98.2 (90.4)
- Num Atoms
- 3096
- Num Waters
- 272
- Num Hetatoms
- 294
- Model mean isotropic B factor (Å2)
- 32.490
- RMSD bond length (Å)
- 0.011
- RMSD bond angle
- 1.289°
- Filename uploaded
- rcsb078221.pdb (uploaded on Mar 19, 2013 11:58 AM)
- Inserted
- May 12, 2009
