Acyl carrier protein synthase

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Revision as of 06:56, 15 July 2012

spinqualitylabelsall models Acyl carrier protein synthase complex with CoA and Mg+2 ion 3hqj Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The crystal structure of Acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) was solved at 1.95 Å. It crystallized as one per asymmetric unit. Since Mtb AcpS has biologically active trimeric arrangement, (in lime, blue, and orange) was constructed using the 3-fold crystallographic symmetry in the P23 space group. The 3′,5′-ADP moieties of the coenzyme A (CoA, colored magenta), are positioned in the cleft between each of two monomers forming three active sites within AcpS trimer. The is formed by the residues D9 (highly conserved), E58, L62, and S65 from monomer A and by R92, P93, R53, H116, and T115 from the neighboring monomer B. The residues labeled and shown as sticks (A and B in the brackets point on the name of the monomer). Hydrogen bonds are shown as dashed lines with interatomic distances in Å. The magnesium (Mg) atoms are shown in spacefill representation and colored in cyan. The CoA is shown in stick representation and colored magenta. Nitrogen and oxygen atoms of the CoA 3′,5′-ADP moiety and of the active site resudues are colored blue and red, respectively. of the structures of the Mtb AcpS trimer (in lime, blue, and orange) and the B. subtilis AcpS trimer (1f7t, in red, cyan, and yellow) reveals that the Mtb AcpS structure is similar to those of other members of group I phosphopantetheine transferase (PPT) family. The is that the extended α3 helix of Mtb AcpS has open conformation. Such open conformation permits to the extended loop of one monomer (lime) to interact with adjacent monomer (blue). The considerably shorter α3 of one B. subtilis AcpS monomer (red) has closed conformation and this doesn't allow interaction with the neighboring monomer (cyan). The B. subtilis AcpS trimer (1f80) three molecules of the acyl carrier protein (ASP). The interactions between B. subtilis AcpS and ACP are predominantly . The B. subtilis AcpS (white) is shown in spacefill representation, the agrinines, lysines, and histidines are colored blue, while aspartates and glutamates are colored red. The ACP molecule (lime) is shown in ribbon representation with aspartates and glutamates as sticks and colored red. The B. subtilis AcpS has large with ASP. of Mtb AcpS surface using the similar orientation as B. subtilis AcpS, shows a moderate electronegative nature in the putative ACP binding site near the ASP 15. The Mtb ASPM structure (1klp, corresponding to ACP) demonstrates considerably lower negative charge. So, the electrostatic interactions between Mtb AcpS and ASPM are, probably, less important.

3D structures of acyl carrier protein synthase

1af8, 2af8, 2kg8, 2kg9, 2kga, 2kgc, 2kgd, 2kge – ScACPS – Streptomyces coelicolor – NMR
2jca - ScACPS
1fte, 1ftf - SpACPS – Streptococcus pneumoniae
1f7l, 1f7t - BsACPS (mutant) – Bacillus subtilis
3f09 - SaACPS – Staphylococcus aureus
3hqj, 3h7q, 3ne1, 3ne3, 3ne9, 3nfd - MtACPS – Mycobacterium tuberculosis
3gwm - ACPS – Mycobacterium smegmatis
3qmn - ACPS – Vibrio cholera

ACPS complex

2jbz - ScACPS + CoA
2wds, 2wdy - ScACPS (mutant) + CoA
2wdo - ScACPS + acetyl-CoA
1fth – SpACPS + ADP
1f80 - BsACPS (mutant) + ACP
2qg8 - ACPS + ADP – Plasmodium yoelii
4dxe - SaACPS + ACP
3hyk - ACPS + ADP – Bacillus anthracis

β-ketoacyl-ACPS

1w0i - AtACPS – Arabidopsis thaliana
2ix4 - AtACPS + hexanoic acid
2c9h, 2iwy, 3hhd – hACPS – human
2iwz - hACPS + hexanoic acid

β-ketoacyl-ACPS I

1dd8, 1g5x, 2buh, 2aq7, 2vb7, 2vb9 - EcACPS I - Escherichia coli
1h4f, 2byw, 2byy, 2bz4 - EcACPS I (mutant)
2wgd - MtACPS I
2wgf - MtACPS I (mutant)
2was - yACPS I PPT domain – yeast
3oyt - ACPS I – Yersinia psetis

ACPS I complex

1fj4, 1fj8, 2aqb, 2vb8 - EcACPS I + antibiotic
2vba - EcACPS I + inhibitor
1ek4 - EcACPS I (mutant) + dodecanoic acid
2bui - EcACPS I + octanoic acid
1f91, 2byx, 2byz, 2bz3 - EcACPS I (mutant) + fatty acid substrate
2wge - MtACPS I + antibiotic
2wgg - MtACPS I (mutant) + antibiotic
2wat - yACPS I PPT domain + CoA

β-ketoacyl-ACPS II

1e5m - ACPS II – Synechocytosis
1j3n - TtACPS II – Thermus thermophilus
1ox0, 1oxh - SpACPS II
2alm, 2rjt - MtACPS II (mutant)
2gqd - SaACPS II
2gp6 - MtACPS II
3e60 – ACPS II – Bartonella henselae
3kzu - ACPS II – Brucella melitensis
3o04 - ACPS II – Listeria monocytogenes
4ddo - BvACPS II – Burkholderia vietnamiensis
1kas, 2gfw – EcACPS II
2gfv - EcACPS II (mutant)

ACPS II complex

1b3n - EcACPS II + antibiotic
2gfx, 3g0y, 3g11, 3hnz, 3ho2, 3ho9, 3i8p - EcACPS II (mutant) + antibiotic
2gfy - EcACPS II (mutant) + dodecanoic acid
4f32 - BvACPS II + antibiotic

β-ketoacyl-ACPS III

1hzp, 1m1m - MtACPS III
1u6e, 2ahb, 2aj9 - MtACPS III (mutant)
1mzj - ACPS III – Streptomyces
1zow, 3il7 - SaACPS III
2ebd - ACPS III – Aquifex aeolicus
3gwa, 3gwe - ACPS III – Burkholderia pseudomallei
4dfe, 4efi - ACPS III – Burkholderia xenovorans
3il3 - ACPS III – Haemophilus influenza
3fk5 - ACPS III – Xanthomonas oryzae
3led - ACPS III – Pseudonomas palustris
2x3e - ACPS III – Pseudonomas aeruginosa
1ebl, 1hn9, 1hnk, 3il9 - EcACPS III

ACPS III complex

1hnd, 1hnh, 2gyo, 2eft - EcACPS III + CoA
1hnj - EcACPS III + malonyl-CoA
2qx1 - EcACPS III + decyl-CoA
1mzs - EcACPS III + inhibitor
1u6s - MtACPS III (mutant) + lauroyl-CoA
21nx, 2qo1 - MtACPS III + undecanoic acid
2qo0 - MtACPS III (mutant) + undecanoic acid
2qnz - MtACPS III + decyl formate
2qny - MtACPS III (mutant) + decyl formate
1ub7 - TtACPS III (mutant)
3il4 - EfACPS III + CoA – Enterococcus faecalis
3il5 - EfACPS III + benzoic acid derivative
3il6 - EfACPS III (mutant) + benzoic acid derivative

References

• Parris KD, Lin L, Tam A, Mathew R, Hixon J, Stahl M, Fritz CC, Seehra J, Somers WS. Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites. Structure. 2000 Aug 15;8(8):883-95. PMID:10997907
• Dym O, Albeck S, Peleg Y, Schwarz A, Shakked Z, Burstein Y, Zimhony O. Structure-function analysis of the acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis. J Mol Biol. 2009 Nov 6;393(4):937-50. Epub 2009 Sep 3. PMID:19733180 doi:10.1016/j.jmb.2009.08.065