PDBsum entry 1bf0

Calcium channel blocker

PDB id: 1bf0

Contents

Protein chain

60 a.a. *

* Residue conservation analysis

PDB id:

1bf0

Name:

Calcium channel blocker

Title:

Calcicludine (cac) from green mamba dendroaspis angusticeps, nmr, 15 structures

Structure:

Calcicludine. Chain: a

Source:

Dendroaspis angusticeps. Eastern green mamba. Organism_taxid: 8618. Other_details: venom

NMR struc:

15 models

Authors:

B.Gilquin,A.Lecoq,F.Desne,M.Guenneugues,S.Zinn-Justin,A.Menez

Key ref:

B.Gilquin et al. (1999). Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine. Proteins, 34, 520-532. PubMed id: 10081964 DOI: 10.1002/(SICI)1097-0134(19990301)34:4<520::AID-PROT11>3.3.CO;2-E

Date:

26-May-98 Release date: 13-Jan-99

Protein chain

P81658  (VKTHC_DENAN) -  Kunitz-type serine protease inhibitor homolog calcicludine from Dendroaspis angusticeps

Seq: 60 a.a.

Struc: 60 a.a.

DOI no: 10.1002/(SICI)1097-0134(19990301)34:4<520::AID-PROT11>3.3.CO;2-E

Proteins 34:520-532 (1999)

PubMed id: 10081964

Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine.

B.Gilquin, A.Lecoq, F.Desné, M.Guenneugues, S.Zinn-Justin, A.Ménez.

ABSTRACT

Calcicludine, a 60-amino acid protein isolated from the green mamba venom, has been recently identified as blocking a large set (i.e., L-, N- and P-type) of Ca2+ channels. The three-dimensional structure of calcicludine has been determined by NMR and molecular modeling using a data set of 723 unambiguous and 265 ambiguous distance restraints, as 33 phi and 13 chi1 dihedral angle restraints. Analysis of the 15 final structures (backbone root-mean-square deviation = 0.6 A) shows that calcicludine adopts the Kunitz-type protease inhibitor fold. Its three-dimensional structure is similar to that of snake K+ channel blockers dendrotoxins. Conformational differences with protease inhibitors and dendrotoxins are localized in the 3(10) helix and loop 1 (segments 1-7 and 10-19), the extremity of the beta-hairpin (segment 27-30), and loop 2 (segment 39-44). These regions correspond to the functional sites of bovine pancreatic trypsin inhibitor (BPTI) and dendrotoxins. The positioning of the N-terminal segment 1-7 relative to the rest of the protein is characteristic of calcicludine. The involvement of this segment and the positively charged K31 at the tip of the beta-hairpin in the biological activity of calcicludine is discussed.

Selected figure(s)

Figure 1.
Figure 1. Sequence of calcicludine (cac) aligned with dendrotoxin K (dtk), -dendrotoxin (dtx), dendrotoxin I (dem), BPTI, amyloid -protein precursor inhibitor (APPI), and ShPI isolated from the Caribbean sea anemone Stichodactyla helianthus. Conserved residues are indicated on the last line (@ : only the hydrophobic character is conserved).

Figure 6.
Figure 6. C -C distances between calcicludine solution structure and eight analogous protein structures: dendrotoxin K (cyan line), -dendrotoxin (purple line), ShPI (yellow line), APPI (black line), BPTI (4pti, 1bpi and 1pit in solid, dashed and dash-dotted red line respectively). to Protein Data Bank[57] entries are indicated in Materials and Methods.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (1999, 34, 520-532) copyright 1999.

Figures were selected by an automated process.