Structure of cobra cardiotoxin CTXI as derived from nuclear magnetic resonance spectroscopy and distance geometry calculations

The structure of cardiotoxin CTX I from Naja naja atra has been investigated by NMR spectroscopy. Sequence specific resonance assignments have been obtained for all backbone protons as well as for most side-chain protons. Distance geometry calculations were carried out using a metric matrix DG program. A total of 715 NOE constraints 27 ∅ angle constraints and a list of the hydrogen bond donors were used for the metric matrix DG calculations and refinement. The average pairwise r.m.s.d. of the resulting structures was 1·01 Å for the backbone heavy atoms, and 1·69 Å for all heavy atoms. The protein is rich in β structure and consists of a large triple-stranded, antiparallel, B sheet as well as and short double-stranded, antiparallel β sheet. Non-regular hydrogen bonding is found between side-chains of the carboxy-terminal end and the rest of the core region. The structure is discussed in terms of evolutionary aspects as well as recent investigations about the biological function and active site.