1A0M

1.1 ANGSTROM CRYSTAL STRUCTURE OF A-CONOTOXIN [TYR15]-EPI

Summary for 1A0M

• Entry DOI: 10.2210/pdb1a0m/pdb
• Descriptor: ALPHA-CONOTOXIN [TYR15]-EPI (2 entities in total)
• Functional Keywords: acetylcholine receptor antagonist, a-conotoxin, neurotoxin
• Biological source: Conus episcopatus
• Cellular location: Secreted: P56638
• Total number of polymer chains: 2
• Total formula weight: 3582.00

Authors

Hu, S.-H.,Loughnan, M.,Miller, R.,Weeks, C.M.,Blessing, R.H.,Alewood, P.F.,Lewis, R.J.,Martin, J.L. (deposition date: 1997-12-03, release date: 1999-01-13, Last modification date: 2024-10-30)

Primary citation

Hu, S.H.,Loughnan, M.,Miller, R.,Weeks, C.M.,Blessing, R.H.,Alewood, P.F.,Lewis, R.J.,Martin, J.L.
The 1.1 A resolution crystal structure of [Tyr15]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods.
Biochemistry, 37:11425-11433, 1998

PubMed Abstract: Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha3beta2 and alpha3beta4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr15]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr15]EpI solved at a resolution of 1.1 A using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo by direct methods. The [Tyr15]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr15]EpI, PnIA, PnIB, and MII, have an alpha4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr15]EpI has the same backbone fold as the other alpha4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr15]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr15]EpI and MII may have different binding modes for the same receptor subtype.

PubMed: 9708977
DOI: 10.1021/bi9806549

Experimental method

X-RAY DIFFRACTION (1.1 Å)