Solution structure of B. subtilis acyl carrier protein

Guang Yi Xu, Amy Tam, Laura Lin, Jeffrey Hixon, Christian C. Fritz, Robert Powers

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background: Acyl carrier protein (ACP) is a fundamental component of fatty acid biosynthesis in which the fatty acid chain is elongated by the fatty acid synthetase system while attached to the 4′-phosphopantetheine prosthetic group (4′-PP) of ACP. Activation of ACP is mediated by holo-acyl carrier protein synthase (ACPS) when ACPS transfers the 4′-PP moiety from coenzyme A (CoA) to Ser36 of apo-ACP. Both ACP and ACPS have been identified as essential for E. coli viability and potential targets for development of antibiotics. Results: The solution structure of B. subtilis ACP (9 kDa) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. A total of 22 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1050 experimental NMR restraints. The atomic rmsd about the mean coordinate positions for the 22 structures is 0.45 ± 0.08 Å for the backbone atoms and 0.93 ± 0.07 Å for all atoms. The overall ACP structure consists of a four α-helical bundle in which 4′-PP is attached to the conserved Ser36 that is located in α helix II. Conclusions: Structural data were collected for both the apo and holo forms of ACP that suggest that the two forms of ACP are essentially identical. Comparison of the published structures for E. coli ACP and actinorhodin polyketide synthase acyl carrier protein (act apo-ACP) from Streptomyces coelicolor A3(2) with B. subtilis ACP indicates similar secondary structure elements but an extremely large rmsd between the three ACP structures (>4.3 Å). The structural difference between B. subtilis ACP and both E. coli and act apo-ACP is not attributed to an inherent difference in the proteins, but is probably a result of a limitation in the methodology available for the analysis for E. coli and act apo-ACP. Comparison of the structure of free ACP with the bound form of ACP in the ACP-ACPS complex reveals a displacement of helix II in the vicinity of Ser36. The induced perturbation of ACP by ACPS positions Ser36 proximal to coenzyme A and aligns the dipole of helix II to initiate transfer of 4′-PP to ACP.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalStructure
Volume9
Issue number4
DOIs
StatePublished - Sep 1 2001

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Acyl Carrier Protein
holo-(acyl-carrier-protein) synthase
Coenzyme A
Fatty Acids

Keywords

  • ACP
  • ACPS
  • Fatty acids biosynthesis
  • NMR
  • Solution structure

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Solution structure of B. subtilis acyl carrier protein. / Xu, Guang Yi; Tam, Amy; Lin, Laura; Hixon, Jeffrey; Fritz, Christian C.; Powers, Robert.

In: Structure, Vol. 9, No. 4, 01.09.2001, p. 277-287.

Research output: Contribution to journalArticle

Xu, GY, Tam, A, Lin, L, Hixon, J, Fritz, CC & Powers, R 2001, 'Solution structure of B. subtilis acyl carrier protein', Structure, vol. 9, no. 4, pp. 277-287. https://doi.org/10.1016/S0969-2126(01)00586-X
Xu, Guang Yi ; Tam, Amy ; Lin, Laura ; Hixon, Jeffrey ; Fritz, Christian C. ; Powers, Robert. / Solution structure of B. subtilis acyl carrier protein. In: Structure. 2001 ; Vol. 9, No. 4. pp. 277-287.
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AU - Xu, Guang Yi

AU - Tam, Amy

AU - Lin, Laura

AU - Hixon, Jeffrey

AU - Fritz, Christian C.

AU - Powers, Robert

PY - 2001/9/1

Y1 - 2001/9/1

N2 - Background: Acyl carrier protein (ACP) is a fundamental component of fatty acid biosynthesis in which the fatty acid chain is elongated by the fatty acid synthetase system while attached to the 4′-phosphopantetheine prosthetic group (4′-PP) of ACP. Activation of ACP is mediated by holo-acyl carrier protein synthase (ACPS) when ACPS transfers the 4′-PP moiety from coenzyme A (CoA) to Ser36 of apo-ACP. Both ACP and ACPS have been identified as essential for E. coli viability and potential targets for development of antibiotics. Results: The solution structure of B. subtilis ACP (9 kDa) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. A total of 22 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1050 experimental NMR restraints. The atomic rmsd about the mean coordinate positions for the 22 structures is 0.45 ± 0.08 Å for the backbone atoms and 0.93 ± 0.07 Å for all atoms. The overall ACP structure consists of a four α-helical bundle in which 4′-PP is attached to the conserved Ser36 that is located in α helix II. Conclusions: Structural data were collected for both the apo and holo forms of ACP that suggest that the two forms of ACP are essentially identical. Comparison of the published structures for E. coli ACP and actinorhodin polyketide synthase acyl carrier protein (act apo-ACP) from Streptomyces coelicolor A3(2) with B. subtilis ACP indicates similar secondary structure elements but an extremely large rmsd between the three ACP structures (>4.3 Å). The structural difference between B. subtilis ACP and both E. coli and act apo-ACP is not attributed to an inherent difference in the proteins, but is probably a result of a limitation in the methodology available for the analysis for E. coli and act apo-ACP. Comparison of the structure of free ACP with the bound form of ACP in the ACP-ACPS complex reveals a displacement of helix II in the vicinity of Ser36. The induced perturbation of ACP by ACPS positions Ser36 proximal to coenzyme A and aligns the dipole of helix II to initiate transfer of 4′-PP to ACP.

AB - Background: Acyl carrier protein (ACP) is a fundamental component of fatty acid biosynthesis in which the fatty acid chain is elongated by the fatty acid synthetase system while attached to the 4′-phosphopantetheine prosthetic group (4′-PP) of ACP. Activation of ACP is mediated by holo-acyl carrier protein synthase (ACPS) when ACPS transfers the 4′-PP moiety from coenzyme A (CoA) to Ser36 of apo-ACP. Both ACP and ACPS have been identified as essential for E. coli viability and potential targets for development of antibiotics. Results: The solution structure of B. subtilis ACP (9 kDa) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. A total of 22 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1050 experimental NMR restraints. The atomic rmsd about the mean coordinate positions for the 22 structures is 0.45 ± 0.08 Å for the backbone atoms and 0.93 ± 0.07 Å for all atoms. The overall ACP structure consists of a four α-helical bundle in which 4′-PP is attached to the conserved Ser36 that is located in α helix II. Conclusions: Structural data were collected for both the apo and holo forms of ACP that suggest that the two forms of ACP are essentially identical. Comparison of the published structures for E. coli ACP and actinorhodin polyketide synthase acyl carrier protein (act apo-ACP) from Streptomyces coelicolor A3(2) with B. subtilis ACP indicates similar secondary structure elements but an extremely large rmsd between the three ACP structures (>4.3 Å). The structural difference between B. subtilis ACP and both E. coli and act apo-ACP is not attributed to an inherent difference in the proteins, but is probably a result of a limitation in the methodology available for the analysis for E. coli and act apo-ACP. Comparison of the structure of free ACP with the bound form of ACP in the ACP-ACPS complex reveals a displacement of helix II in the vicinity of Ser36. The induced perturbation of ACP by ACPS positions Ser36 proximal to coenzyme A and aligns the dipole of helix II to initiate transfer of 4′-PP to ACP.

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