### Abstract

The three-dimensional structure of the sea anemone polypeptide Stichodactyla helianthus neurotoxin I in aqueous solution has been determined using distance geometry and restrained molecular dynamics simulations based on NMR data acquired at 500 MHz. A set of 470 nuclear Overhauser enhancement values was measured, of which 216 were used as distance restraints in the structure determination along with 15 dihedral angles derived from coupling constants. After restrained molecular dynamics refinement, the eight structures that best fit the input data form a closely related family. They describe a structure that consists of a core of twisted, four-stranded, antiparallel β-sheet encompassing residues 1-3, 19-24, 29-34, and 40-47, joined by three loops, two of which are well defined by the NMR data. The third loop, encompassing residues 7-16, is poorly defined by the data and is assumed to undergo conformational averaging in solution. Pair-wise root mean square displacement values for the backbone heavy atoms of the eight best structures are 1.3 ± 0.2Å when the poorly defined loop is excluded and 3.6 ± 1.0Å for all backbone atoms. Refinement using restrained molecular dynamics improved the quality of the structures generated by distance geometry calculations with respect to the number of nuclear Overhauser enhancements violated, the size of the total distance violations and the total potential energies of the structures. The family of structures for S. helianthus neurotoxin I is compared with structures of related sea anemone proteins that also bind to the voltage-gated sodium channel.

Original language | English |
---|---|

Pages (from-to) | 13016-13028 |

Number of pages | 13 |

Journal | Journal of Biological Chemistry |

Volume | 265 |

Issue number | 22 |

Publication status | Published - 5 Aug 1990 |

Externally published | Yes |

### Cite this

*Journal of Biological Chemistry*,

*265*(22), 13016-13028.

}

*Journal of Biological Chemistry*, vol. 265, no. 22, pp. 13016-13028.

**Solution structure of neurotoxin I from the sea anemone Stichodactyla helianthus : A nuclear magnetic resonance, distance geometry, and restrained molecular dynamics study.** / Fogh, Rasmus H.; Kem, William R.; Norton, Raymond S.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Solution structure of neurotoxin I from the sea anemone Stichodactyla helianthus

T2 - A nuclear magnetic resonance, distance geometry, and restrained molecular dynamics study

AU - Fogh, Rasmus H.

AU - Kem, William R.

AU - Norton, Raymond S.

PY - 1990/8/5

Y1 - 1990/8/5

N2 - The three-dimensional structure of the sea anemone polypeptide Stichodactyla helianthus neurotoxin I in aqueous solution has been determined using distance geometry and restrained molecular dynamics simulations based on NMR data acquired at 500 MHz. A set of 470 nuclear Overhauser enhancement values was measured, of which 216 were used as distance restraints in the structure determination along with 15 dihedral angles derived from coupling constants. After restrained molecular dynamics refinement, the eight structures that best fit the input data form a closely related family. They describe a structure that consists of a core of twisted, four-stranded, antiparallel β-sheet encompassing residues 1-3, 19-24, 29-34, and 40-47, joined by three loops, two of which are well defined by the NMR data. The third loop, encompassing residues 7-16, is poorly defined by the data and is assumed to undergo conformational averaging in solution. Pair-wise root mean square displacement values for the backbone heavy atoms of the eight best structures are 1.3 ± 0.2Å when the poorly defined loop is excluded and 3.6 ± 1.0Å for all backbone atoms. Refinement using restrained molecular dynamics improved the quality of the structures generated by distance geometry calculations with respect to the number of nuclear Overhauser enhancements violated, the size of the total distance violations and the total potential energies of the structures. The family of structures for S. helianthus neurotoxin I is compared with structures of related sea anemone proteins that also bind to the voltage-gated sodium channel.

AB - The three-dimensional structure of the sea anemone polypeptide Stichodactyla helianthus neurotoxin I in aqueous solution has been determined using distance geometry and restrained molecular dynamics simulations based on NMR data acquired at 500 MHz. A set of 470 nuclear Overhauser enhancement values was measured, of which 216 were used as distance restraints in the structure determination along with 15 dihedral angles derived from coupling constants. After restrained molecular dynamics refinement, the eight structures that best fit the input data form a closely related family. They describe a structure that consists of a core of twisted, four-stranded, antiparallel β-sheet encompassing residues 1-3, 19-24, 29-34, and 40-47, joined by three loops, two of which are well defined by the NMR data. The third loop, encompassing residues 7-16, is poorly defined by the data and is assumed to undergo conformational averaging in solution. Pair-wise root mean square displacement values for the backbone heavy atoms of the eight best structures are 1.3 ± 0.2Å when the poorly defined loop is excluded and 3.6 ± 1.0Å for all backbone atoms. Refinement using restrained molecular dynamics improved the quality of the structures generated by distance geometry calculations with respect to the number of nuclear Overhauser enhancements violated, the size of the total distance violations and the total potential energies of the structures. The family of structures for S. helianthus neurotoxin I is compared with structures of related sea anemone proteins that also bind to the voltage-gated sodium channel.

UR - http://www.scopus.com/inward/record.url?scp=0025323374&partnerID=8YFLogxK

M3 - Article

VL - 265

SP - 13016

EP - 13028

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 22

ER -