PDBsum entry 1imt

Toxin

PDB id: 1imt

Contents

Protein chain

80 a.a. *

* Residue conservation analysis

PDB id:

1imt

Name:

Toxin

Title:

Mamba intestinal toxin 1, nmr, 39 structures

Structure:

Intestinal toxin 1. Chain: a. Synonym: mit1

Source:

Dendroaspis polylepis polylepis. Black mamba. Organism_taxid: 8620. Strain: polylepis. Secretion: venom

NMR struc:

39 models

Authors:

J.Boisbouvier,J.-P.Albrand,M.Blackledge,M.Jaquinod,H.Schweitz, M.Lazdunski,D.Marion

Key ref:

J.Boisbouvier et al. (1998). A structural homologue of colipase in black mamba venom revealed by NMR floating disulphide bridge analysis. J Mol Biol, 283, 205-219. PubMed id: 9761684 DOI: 10.1006/jmbi.1998.2057

Date:

14-Apr-98 Release date: 20-Apr-99

Protein chain

P25687  (MIT1_DENPO) -  Toxin MIT1 from Dendroaspis polylepis polylepis

Seq: 81 a.a.

Struc: 80 a.a.

DOI no: 10.1006/jmbi.1998.2057

J Mol Biol 283:205-219 (1998)

PubMed id: 9761684

A structural homologue of colipase in black mamba venom revealed by NMR floating disulphide bridge analysis.

J.Boisbouvier, J.P.Albrand, M.Blackledge, M.Jaquinod, H.Schweitz, M.Lazdunski, D.Marion.

ABSTRACT

The solution structure of mamba intestinal toxin 1 (MIT1), isolated from Dendroaspis polylepis polylepis venom, has been determined. This molecule is a cysteine-rich polypeptide exhibiting no recognised family membership. Resistance to MIT1 to classical specific endoproteases produced contradictory NMR and biochemical information concerning disulphide-bridge topology. We have used distance restraints allowing ambiguous partners between S atoms in combination with NMR-derived structural information, to correctly determine the disulphide-bridge topology. The resultant solution structure of MIT1, determined to a resolution of 0.5 A, reveals an unexpectedly similar global fold with respect to colipase, a protein involved in fatty acid digestion. Colipase exhibits an analogous resistance to endoprotease activity, indicating for the first time the possible topological origins of this biochemical property. The biochemical and structural homology permitted us to propose a mechanically related digestive function for MIT1 and provides novel information concerning snake venom protein evolution.

Selected figure(s)

Figure 5.
Figure 5. Solution structure of MIT1. (a) Backbone and disulphide-bridge heavy atoms from residues 5 to 80 of the 39 NMR conformers (calculations rMD, Table 1). N, C and C^a atoms from residues 6 to 79 of each structure were superimposed on the average structure atoms. Central core residue backbone atoms (5 to 10, 16 to 21, 29 to 43, 57 to 69 and 75 to 80) are displayed in blue, extremity residue backbone atoms of each finger (11 to 15, 22 to 28, 44 to 56 and 70 to 74) are displayed in red, and disulphide-bridges in yellow. (b) Stereo view of the conformer closest to the mean structure of the 39 conformers shown in (a). The following colours were used for the side-chains: blue, Arg and Lys; red, Glu and Asp; yellow, Ala, Cys, Ile, Leu, Met, Phe, Pro, Trp and Val; grey, Asn, Gln, Ser, Thr and His. Buried side-chains of the inner ionic bridge; Asp10 and Arg54 are displayed with a thicker stick and are labelled. The His46 O atom is labelled.

Figure 9.
Figure 9. Electrostatic potentials map of colipase and MIT1. (a) and (b) The exposed surface of colipase, (c) and (d) were coloured with the electrostatic potential [Gilson et al 1987] by linear interpolation between red (f(r)< -3 kT, negative), white (f(r = 0 kT, neutral) and blue (f(r)>3 kT, positive). (a) and (c) Surfaces were displayed with the same orientation as Figure 5. (b) and (d) Representations were turned by 180° with respect to the vertical axis.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 283, 205-219) copyright 1998.

Figures were selected by an automated process.