1AGG

THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTA

Summary for 1AGG

• Entry DOI: 10.2210/pdb1agg/pdb
• Descriptor: OMEGA-AGATOXIN-IVB (1 entity in total)
• Functional Keywords: neurotoxin, p-type calcium channel antagonist
• Biological source: Agelenopsis aperta
• Cellular location: Secreted: P37045
• Total number of polymer chains: 1
• Total formula weight: 5287.13

Authors

Reily, M.D.,Thanabal, V.,Adams, M.E. (deposition date: 1995-11-03, release date: 1996-03-08, Last modification date: 2024-11-13)

Primary citation

Reily, M.D.,Thanabal, V.,Adams, M.E.
The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.
J.Biomol.NMR, 5:122-132, 1995

PubMed Abstract: The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel.

PubMed: 7703698
DOI: 10.1007/BF00208803

Experimental method

SOLUTION NMR